Cancer Therapeutics Training Program

Currently accepting applications. 

The deadline to apply is April 15, 2024.

The mission of the NIH-funded CT² program is to train the next generation of leaders in the field of oncology drug and diagnostic development.  It is open to both PhDs and MDs and the training consists of 2 years of mentored research (clinical or laboratory). The CT² program provides training focused on acquiring a thorough understanding of cancer biology and the drug development progress to position graduates for careers in either academic or industrial oncology drug/diagnostics development.

Please direct inquiries Amy Spilkin PhD at aspilkin@health.ucsd.edu.

INTRODUCTION

The development of better therapeutic agents for the treatment of cancer is a high priority research goal for the next 20 – 30 years. Major advances in cell and molecular biology, genetics and genomics, structural and computational biology and medicinal chemistry have provided the tools needed to identify critical targets, validate their importance to cellular function, design drugs and clinical trials and identify patient populations most likely to benefit from treatment. To capitalize on these advances it is essential for institutions of higher learning to train scientists and physician-scientists in the skills needed to execute successful drug development programs. There is also urgent need to make this development process far more efficient. This will require that scientists and physicians be trained to use new technologies and paradigms that can be innovatively integrated to overcome long-standing barriers in the process of moving a drug from discovery through clinical trials to a successful new drug application (NDA). There is a severe shortage of professionals trained to effectively manage the various stages of the development of a cancer drug, and particularly to manage the overall process.  The Cancer Therapeutics Training Program (CT²) aims to address this challenge by providing scientists, physicians, and clinicans with an intensive two-year period of post-doctoral training in developmental therapeutics focused on cancer drugs. CT² fellows are mentored by individuals from both academia and industry who are national leaders in each part of the development process. This training will take place in an NCI-designated Comprehensive Cancer Center whose research programs encompass each of the major steps in the drug development process and which is engaged in the discovery and testing of a wide spectrum of novel cancer drugs and drug-delivery systems.

Academic Environment

The UC San Diego Moores Cancer Center provides a superb crucible for the operation of a cohesive developmental therapeutics training program. It is located in the middle of one of the largest concentrations of biotechnology and pharmaceutical companies in the world, with over 470 large and small companies dedicated to developing new therapeutics in its immediate environment. There is extensive interaction between the Cancer Center faculty and professionals in the surrounding companies skilled in the art of drug development, providing a highly innovative setting within which to train the next generation of scientists and physician-scientists to lead academic drug development efforts into the future.

The Rebecca and John Moores Cancer Center

The UC San Diego Cancer Center was founded in 1979. Its growth has been fostered by the rich fabric of intellectual and entrepreneurial prowess for which San Diego has become famous. The Cancer Center has an administrative structure of seven Research Programs and 12 Shared Resources. The clinical faculty of the Center provides state-of-the-art cancer care within the context of a major clinical trials and translation research program. The Cancer Center sponsors multiple seminars, journal clubs, colloquia and meetings in which research progress is discussed. In 2006, the Center opened a 270,000 sq. ft. multipurpose building that houses all of the cancer outpatient clinical services and provides a large amount of laboratory research space. This facility brings together–both physically and programmatically–laboratory-based scientists, epidemiologists and clinical oncologists to effectively foster translational cancer research.

More than 400 new patients enter clinical treatment protocols annualy at the Cancer Center. This includes NCI Cooperative Group trials (CALGB, NSABP, RTOG and GOG) as well as investigator-initiated trials.  More than 50% of the patients are entered on institutionally generated protocols. There are 3 inpatient teaching hospitals, each of which offers a set of unique characteristics: These include the UC San Diego Medical Center (UCSDMC) in the Hillcrest region of San Diego, the VA Medical Center (VAMC) in La Jolla, and Jacobs Medical Center in La Jolla.  UCSDMC is a 403-bed primary, secondary and tertiary care university hospital. The inpatient hospital population is equally divided between male and female patients. There is a 10-bed NIH-funded Clinical Research Center at which complex phase I and phase II protocols, including pharmacokinetic studies, are performed. A GCRC satellite facility operates in the new Moores Cancer Center facility adjacent to the Thornton Hospital. The VAMC has 238 beds, occupied primarily by men. There is a large cohort of patients who receive primary care under the auspices of the VA (approximately 25,000, of which 600 carry a diagnosis of AIDS), and a large number of both inpatient and outpatient consultations in Hematology-Oncology are requested.  Jacobs Medical Center has 245 beds and is a UCSD hospital. The blood and marrow transplant program (BMT) is housed at Jacobs Medical Center, and offers exposure to both autologous and allogeneic transplant procedures. Research facilities include the Cancer Center, Clinical Sciences Building, Center for Molecular Genetics, Center for Molecular Medicine, Leichtag Biomedical Research Building and the Veterans Administration Medical Center on the La Jolla campus.

The Biomedical and Pharmaceutical Community

A number of other leading biomedical research institutes with highly active cancer research and drug development programs are located immediately adjacent to the UC San Diego campus and the Moores Cancer Center building in La Jolla. These include the Salk Institute, the Scripps Research Institute, the Sanford-Burnham Institute (formerly La Jolla Cancer Research Foundation), the La Jolla Institute of Allergy and Immunology, the Medical Biology Institute, and the La Jolla Institute of Experimental Medicine. The close physical proximity of these institutions to UC San Diego and to one another creates a remarkable concentration of biomedical research talent that is second to none in the world. UC San Diego is an NCI-designated Comprehensive Cancer Center; two of the other immediately adjacent institutes (the Salk Institute and the Sanford-Burnham Institute) are NCI-designated Basic Cancer Research Centers. Fostered in part by proximity and in part by common research interests, the faculty of these institutions are involved in an extensive network of collaborative interactions, many of which are supported by joint grants and dual appointments between the institutions.

In addition to having a leading research university surrounded by an outstanding set of independent biomedical research institutes, the cancer drug development efforts of the Cancer Center are fostered by an extraordinary community of biomedical and biotechnology companies that surround the campus. Ranked third in the nation in the number of established biotech companies, San Diego’s life science community has become a model for the rapidly growing biotech and biopharm industry. Well established since the 1980s, these industries continue to expand annually and such stability attracts both startups and new talent nationwide. The path to success in the world of biotech and biopharmaceuticals requires access to outstanding universities, generous venture capital, and large amounts of Federal funding. San Diego boasts all of these ingredients, enabling it to maintain a leadership position in the development of new cancer therapeutics. San Diego biotech companies currently have >200 products in development. What distinguishes San Diego from other cities is the established support structure and the availability of experienced professionals to guide the rapid growth of the biopharmaceutical and biotechnology industries.  The establishment of innovative partnerships between the public and private sectors, for which UC San Diego has become famous, facilitates the development of truly novel therapeutic paradigms. A key component of the training program proposed in this application involves practical training through interaction with industry leaders and well as University-based mentors.

PROGRAM OVERVIEW

• Didactic Training
• Fellowship Stipend and Benefits
• Travel

The CT² Program provides a 2 year period of training in developmental therapeutics for  post-doctoral scientists and physician-scientists at the Moores Cancer Center at UC San Diego Health.  The focus is on the development of novel therapeutics of all types combined with identification of biomarkers that allow individualization of treatment. The mission is to train investigators in each of the major steps in the development of a novel cancer therapeutic so as to position these individuals to play leading roles in academic institutions and industry in translating laboratory-based discoveries into safe and effective cancer therapeutic agents.

The training program has a single track for both PhD and MD scientists.  Irrespective of whether an individual’s past training and expertise is most relevant to an early (e.g., target identification/validation) or late (e.g., Phase I – III clinical trials) step in drug development, there is a core body of knowledge about the process of drug development that must be mastered by any person aiming to become a leader in cancer therapeutics.  The training program has three components: 1) the completion of formal didactic courses that cover key tools and skills needed in the drug development process; 2) the conduct of a drug development research project under the direction of a faculty mentor; and, 3) participation in lecture series including presentations from UCSD faculty and speakers from pharmaceutical companies developing cancer therapeutics and diagnostics.  Trainees are expected to attend Cancer Center and other institutional seminars, workshops and journal clubs and attend the annual American Association for Cancer Research or equivalent national meeting.  Clinically trained fellows will not have clinical responsibilities beyond what may be required by their individual training program. Clinical fellows will be offered the opportunity, on a voluntary basis, to have a half-day clinic in their subspecialty each week.

Hands On Research Training

Fellows will conduct a project of their choice continuously during the 2 year period under the mentorship of a CT² faculty member. The project may be focused on any of the following steps in the drug discovery process:

• Target identification, validation, function
• Drug design or synthesis
• Development or application of informatics or computational tools related to therapeutics development
• Development or use of novel animal models for pre-clinical testing
• Development or use of molecular or imaging diagnostic tools that can guide drug development
• Identification of lead compounds and investigation of structure activity relationships
• Cellular pharmacology and testing of in vitro activity in cell line models
• Pharmacogenomics and genetic determinants of drug sensitivity and toxicity
• Development of analytical tools for drug measurement in biological fluids
• Efficacy in animal tumor models
• Pharmacokinetics in animal models
• Preclinical non-GLP toxicology and toxicogenetics
• Identification of biomarkers that quantify or predict drug effect
• Design and execution of Phase I clinical trials of novel agents
• Design and execution of human pharmacokinetic trials
• Design and execution of Phase II clinical trials of novel agents
• Design and execution of Phase III clinical trials

In addition to providing individualized guidance to the trainee, the Mentor is a source of advice for the development of the individual’s career path.  Within the first 3 months, each trainee will prepare a 5-page project plan, to be reviewed by the CT² Executive Committee. The final plan will serve as the basis for assessing progress and performance throughout the 2 year period.  There will be two formal reviews of each trainee’s progress during the training period, in month 8 and month 20, consisting of a presentation of research progress and feedback from the Executive Committee for the educational benefit of the trainee.

Didactic Training

CREST Coursework
CT² trainees are required to complete 5 courses offered through the Clinical Research Enhancement through Supplemental Training (CREST) program, designed to be delivered over the 2 year training period (see Requirements). A different module is offered in each quarter; each module consists of 10 weekly, 2 hour periods of instruction in the late afternoon or early evening. The modules cover basic principles of cancer drug developmental therapeutics, biostatistics, data management and informatics, clinical trial design and execution, regulatory affairs, patient oriented research and epidemiology. A Certificate in Clinical Research and/or a Masters Degree in Advanced Studies in Clinical Research, are also available upon completion of this introductory curriculum with minor additions.

Ethics Requirement
Trainees are required to take one program-approved Ethics course offered during the Fall, Winter and Spring quarters through the Research Ethics Program. This course satisfies the NIH requirement for instruction in the responsible conduct of research. Topics include roles and responsibilities of researchers, data collection and ownership, issues relating to use of animal and human subjects, scientific and grant writing, code of ethics for authors, reviewers and editors and conflicts of interest.

Seminars and Lectures
Trainees are expected to participate in 2 formal seminar programs:

• Topics in Cancer Drug Development (see Lecture Schedule): A weekly seminar series during the Fall, Winter and Spring quarters featuring talks on topics directly relevant to cancer therapeutics and diagnostics development by UCSD faculty and presentations by senior leaders in our biomedical/pharmaceutical company community on the drugs they are developing.
• Cancer Center Lecture Series:  A bi-monthly meeting where national leaders in cancer research discuss issues and challenges.

Trainees may also participate in the Topics in Hematology-Oncology weekly lecture series that features Faculty members and Fellows lecturing on the clinical use of cancer therapeutic agents and the management of cancer.

Each trainee will be invited to present a seminar to the Faculty and Trainees of the CT2 Program each year.

Grant Writing

The ability to prepare a cogent and clearly written research proposal is essential to the trainee’s ability to assume a leadership position in cancer drug development in academia or industry. Within the first 18 months, trainees are required to prepare a mock NIH application which will is critiqued by an ad hoc group of faculty members, acting as a typical Study Section, and provide written feedback to the fellow.

Career Preparation

After completion of this Fellowship, trainees will be equipped with a broad range of skills vital to careers as independent investigators in Academia or leaders in the pharmaceutical industry. Under the direction of a  faculty Mentor, the trainee is expected acquire critical investigative skills in his/her focused area of research. In addition, the trainee will acquire practical experience within the field of developmental therapeutics and diagnostics.

Fellowship Stipend and Benefits

Your CT² stipend level will be determined by the number of full years of training that you have completed since receiving your terminal/professional degree. The stipend is based on the NIH stipend scale and is not determined by the CT² program or UC San Diego. You are eligible for a stipend increase following successful completion of your first 12 months of appointment.

The benefits of the program include HMO medical, dental and vision insurance coverage for yourself and your dependents.

Travel

A $1,000 annual travel stipend will be provided for you to attend the annual meeting of the American Association of Cancer Research or a similar conference.

Laboratory Supplies

The mentor in whose laboratory you will be working will provide research equipment, supplies and lab space for your entire training period during which you will be executing your research project.

Housing

Housing is not included in the CT² award. Appointed trainees are encouraged to arrange for housing immediately upon acceptance, as housing is in high demand in areas close to the La Jolla campus. Faculty and staff housing information can be accessed at offcampushousing.ucsd.edu. The UC San Diego La Jolla Del Sol Office (Phone: (858) 587-1221 E-mail: ljds@ucsd.edu) compiles a market comparison report which provides information regarding off-campus apartment complexes in the UTC area of La Jolla.  This report can be accessed through UC San Diego Housing.

PROGRAM FACULTY

All program faculty are members of  Moores Cancer Center at UC San Diego Health. They represent 10 academic Departments (Cell & Molecular Medicine Program, Center For Marine Biotechnology & Biomedicine, Chemistry and Biochemistry, Division of Biological Sciences, Medicine, Nanoengineering, Pathology, Pediatrics, Pharmacology and Surgery) and 4 organized research units (Moores Cancer Center, Scripps Institution of Oceanography, Ludwig Institute for Cancer Research, and the Center for Cancer Nanotechnology Excellence). The 20 participating faculty constitute a group of extremely productive investigators who are major leaders in their respective fields. All faculty mentors have agreed to participate in the Program’s courses and seminars, to accept trainees into their laboratories and research programs, and to provide career guidance to trainees. The faculty have been carefully selected so as to bring expertise in all phases of drug development to the Program.

Michael Bouvet, MD, Professor of Surgery & CT2 Program MPI (Contact). Dr. Bouvet is a surgical oncologist  with expertise in the management of pancreatic, thyroid, parathyroid, adrenal, and the major GI cancers. His  research interests include the testing of novel drugs in orthotopic models of pancreatic cancer, as well as the  use of novel fluorescent probes for intra-operative imaging of these tumors. His laboratory developed and  validated the use of fluorophore-conjugated antibodies for surgical navigation and laparoscopic localization of  gastrointestinal tumors and pioneered the use of photoimmunotherapy to reduce recurrence after surgical  resection. He is currently a co-Investigator in a phase I trial of a novel fluorescent nerve imaging (ALM-488)  agent and the Chair of the Data Safety Committee for a multicenter trial phase III trial of SGM-101, a fluorescently  conjugated anti-CEA antibody used during colorectal cancer surgery. Dr. Bouvet has previously mentored 6 CT2 trainees who have collectively published over 85 peer reviewed articles stemming from their training. 

Joseph Califano, MD, Professor of Surgery and Physician in Chief. Dr. Califano is an internationally recognized  physician-scientist who has translated multiple discoveries from his own laboratory into the clinic, including  detection of HPV-related and other head and neck cancers. He is the Director of the Head and Neck Cancer  Center, Moores Cancer Center at UC San Diego Health. His major focus is the clinical practice of head and  neck surgical oncology and the integration of basic, molecular biologic research in that practice. Dr. Califano  directs an NIH-funded laboratory investigating the molecular biologic basis of head and neck cancer. He has  published over 300 articles related to both the clinical and basic scientific aspects of cancer, and currently serves  as a member of the NCI Head and Neck Steering Committee, is a Council Member of the American Head and  Neck Society, and is on the NCCN Board of Directors. 

Hannah Carter, PhD, Associate Professor of Medicine, Medical Genetics. Dr. Carter’s lab focuses on integrating  information from protein structure and protein interactions, to develop new tools to prioritize protein-interactions  as therapeutic targets and to understand why different mutations on the same driver gene confer different drug  sensitivities. They are investigating the molecular pathways that underlie cancer cell motility behaviors to identify  therapeutic strategies that might prevent cancer cells from adopting invasive or metastatic behaviors. In addition,  they study the relationships between inherited genetic variation, tumor genomes, and the tumor immune  microenvironment to understand mechanisms of immune suppression and evasion. The research goal is to  uncover new therapeutic targets to reinvigorate the host anti-tumor immune response. 

Yuan Chen, PhD, Professor of Surgery. The long-term objective of Dr. Chen’s laboratory is to address novel  mechanisms that can be targeted for developing innovative treatments for cancer using multidisciplinary  approaches. For more than two decades, her research has focused on ubiquitin-like (Ubl) modifications, the  regulation of which influences major oncogenic pathways, such as c-Myc and KRas-dependent oncogenesis,  and antiviral and antitumor response. Current research interests include investigation of the mechanism by  which SUMOylation regulates KRas activation in pancreatic cancers, elucidating the regulatory network that  controls KRas SUMOylation, and investigating the efficacy of SUMO E1 inhibitors in suppressing proliferation of  pancreatic cancer growth in preclinical mouse models.  

David Cheresh, PhD, Distinguished Professor of Pathology. Dr. Cheresh has made fundamental discoveries  on the role that gangliosides, integrins, growth factor receptors, and intracellular kinases play in tumor growth  and vascular remodeling. His early work focused on the functional role of the gangliosides in neuroectodermal  tumors, leading to the discovery that anti-GD2 monoclonal inhibited the growth of preclinical neuroblastoma  tumors. This antibody was humanized (Unituxin), clinically active in patients with neuroblastoma, and in 2015  was approved by the FDA as a front-line therapy for this disease. Cheresh discovered that integrin αvβ3 is  specifically expressed on angiogenic endothelial cells, where it contributes to the growth of tumor-associated  blood vessels and plays a role in the progression of various cancers. Cheresh’s research has been widely cited: 12 peer-reviewed publications have been cited >1,000 times. Cheresh has developed antibodies, kinase  inhibitors, and nanoparticles now in clinical development in patients with cancer. He has founded a number of  Biotech start-ups including TargeGen, which developed the JAK2 specific drug Fedratinib, approved by FDA for  myeloproliferative disorders in August 2019.  

Napoleone Ferrara, MD, Professor of Pathology. Dr. Ferrara is the Senior Deputy Director for Basic Science  at the Moores Cancer Center. The Ferrara lab studies the biology of angiogenesis and the identification of its  regulators. Dr. Ferrara reported the isolation and cDNA cloning of vascular endothelial growth factor (VEGF) that led to the development of bevacizumab (during his leadership years at Genentech). The Ferrara lab is now  investigating mechanisms of tumor angiogenesis, alternatives to VEGF, in particular the role of factors produced  by myeloid cells and fibroblasts.  

Pradipta Ghosh, MD, Professor of Medicine. The Ghosh lab investigates how “rheostats,” or specific signaling  nodes that serve as critical hubs within pathologic signaling networks, act to drive malignancies. She has helped  identify nodes at which multiple signal pathways converge upon multi-modular rheostat proteins that shape entire  disease networks via modulation of trimeric G proteins. She has discovered novel interfaces assembled at the  crossroads of G protein and growth factor signaling pathways and assessed their significance as potential  therapeutic targets. Dr. Ghosh has successfully mentored 1 past and 1 current CT2 trainee. Dr. Ghosh currently  serves as a member of the CT2 Executive Committee. 

Ananda Goldrath, PhD, Professor of Molecular Biology. Dr. Goldrath and her team have identified a unique  role for the transcription factor Runx3 in controlling the TRM gene-expression program in TIL wherein  overexpression of Runx3 in tumor-specific T cells enhances adoptive therapy efficacy in mouse models of  melanoma. Exploiting the features of TRM may be ideal for enhancing CD8 T cell accumulation and activity in  solid tumors. Recent studies show that human TIL can be TRM-like, and their presence can predict improved  prognoses in breast and lung cancer patients. One of her principal goals is to identify regulators of anti-tumor  immunity and TRM via understanding their metabolic adaptations to tissues. Harnessing or targeting memory T  cells through direct manipulation of transcriptional or metabolic activity is a novel strategy for optimizing  prophylactic or therapeutic immunity. Dr. Goldrath is one of the newest faculty members of the CT2. 

Catriona Jamieson, MD, PhD, Professor of Medicine, Deputy Director of Moores Cancer Center, Koman Family  Presidential Endowed Chair in Cancer Research, Director of the Sanford Stem Cell Clinical Center. Dr.  Jamieson, a stem cell biologist and clinically active hematologist, has made transformative clinical impact  translating two practice-changing discoveries made in her lab to FDA approvals in the last year. Her highly cited  pioneering research has focused on understanding the molecular drivers of pre-cancer stem cell transformation into CSCs. She and her team discovered that the JAK2 mutation, typical of myeloproliferative neoplasms,  occurred in hematopoietic stem cells that could be selectively targeted with a JAK2 inhibitor, Fedratinib  (Inrebic®), leading to clinical trials for which she served as a PI, and recent FDA approval. Subsequently, she  and her team discovered that JAK2 signaling activated the RNA deaminase, ADAR1, resulting in malignant self renewal and revealing RNA editing based biomarkers of CSC generation. Her team showed that CSC  maintenance was dependent on hedgehog signaling and could be selectively targeted with glasdegib  (Daurismo®) pre-clinically and in clinical trials (which she led) resulting in FDA approval for acute myeloid  leukemia (AML) in the elderly. Dr. Jamieson identified splicing deregulation during progression to AML as a key  therapeutic vulnerability and developed a splicing modulator 17S-FD-895 in a ‘cancer interception’ paradigm. 

Michael Karin, PhD, Distinguished Professor of Pharmacology. Dr. Karin’s research is focused on  understanding how inflammation and metabolism contribute to cancer onset, metastatic spread, and response  to therapy. His lab conducts studies with mouse models and human clinical specimens, when available, and  mainly focus on liver, pancreas, and colorectal cancer. The inflammatory input that impacts tumor initiation,  promotion, progression, and spread can be generated outside the cancer and exerted via the tumor  microenvironment (TME) or originate within the cancer cell and affect the TME, resulting in a feedforward loop.  Likewise, metabolic derangements and stress that contribute to tumor initiation and progression can be exerted  from outside or inside the tumor. Dr. Karin was the most cited scientist in the world in 2000; he has remained one of the most highly cited for the past 20 years.  

Irina Kufareva, PhD, Associate Professor of Pharmacy and Pharmaceutical Sciences. The goal of Dr. Kufareva’s research is understanding cellular responses to stimuli and drugs, from atomic-resolution molecular  interactions to the level of cellular systems, using methods and tools of data-driven trans-scale computational  biology. GPCRs and G proteins, the two key classes of cell signaling molecules, have been the main focus of  recent work. Combined with collaborators, the lab was able to elucidate the structural basis of ligand binding  and signaling in chemokine GPCRs CXCR4 and ACKR3 (both playing a central role in progression and  metastasis of numerous cancers, CCR5, and CCR2). The lab has also made key contributions to understanding  non-receptor activation of heterotrimeric G proteins and has solved the first structure of a G protein complexed  with one such activator. The lab’s newest direction involves building and applying data-driven network-based  models of cell signaling in order to decode and predict signaling responses downstream of selected cancer associated receptors, and to bridge the gap between molecular and cellular level phenomena.  

Andrew Lowy, MD, Professor of Surgery, Division Chief of Surgical Oncology and Director of Surgical Oncology  at MCC. Dr. Lowy is co-leader of the Stand Up to Cancer Pancreatic Cancer Interception Dream Team, along  with Dr. Tannishtha Reya. His laboratory focuses on understanding the drivers of pancreatic cancer progression, as well as identifying and testing new targets for pancreatic cancer therapy using a variety of model systems  including 2D and 3D (organoid) culture systems, patient-derived xenografts, and genetically engineered mouse  models. Current areas of active work include studies of 1) the MST1R kinase in immunomodulation, 2) novel  regulators of actin dynamics and 3) pancreatic cancer stem cell dependencies. Dr. Lowy has successfully  mentored 3 CT2 trainees. 

Alexandra Newton, PhD, Distinguished Professor of Pharmacology. Dr. Newton runs a multidisciplinary Protein  Kinase C and Cell Signaling Biochemistry and Cell Biology Research Group in the School of Medicine,  investigating molecular mechanisms of signal transduction in the Phospholipase C (PLC) and Phosphoinositide  3-kinase (PI3 kinase, or PI3-K) signaling pathways. She has been continuously funded by the NIH since 1988.  Newton has published over 190 peer-reviewed research articles that have been cited more than 25,000 times,  been awarded 1 patent, and co-edited two books on protein biochemistry and PKC. Her work straddles basic  research and has illuminated understanding of PKC ß as a tumor suppressor in human cancers. 

Tariq Rana, PhD, Professor of Pediatrics, Head of Genetics and Vice Chair for Innovation in Therapeutics. Dr.  Rana’s research focuses on elucidating the function of regulatory RNAs, and his team has helped to uncover  the fundamental roles of RNAs and RNA-protein complexes in gene silencing, stem cell biology, cancer, and  host-pathogen interactions and immunity. The common thread running through all aspects of his research is his  passion to reveal the architecture and function of RNA regulatory machines and their role in modulating biological  functions. The multidisciplinary nature of his work has allowed his team to launch collaborations with  investigators working in chemistry, biology, and drug discovery. Several technologies developed by his group  have been used to develop small molecules and biological therapeutics that are currently in clinical trials. Rana  has mentored several highly successful former trainees. 

Tannistha Reya, PhD, Professor of Pharmacology. Dr. Reya’s research focuses primarily on defining the  signals that control self-renewal of stem cells, and how they are subverted to drive cancer progression. Her lab  has identified multiple signals such as the Wnt, Hh and Msi pathways as critical for cancer stem cell maintenance  and disease progression in hematologic malignancies. Her work that antagonists of Hedgehog signaling can  block the propagation of normal and drug resistant CML in part formed the basis for the approval of Hh  antagonists in acute myeloid leukemia. Reya is also a member of the stand up to cancer pancreatic cancer  dream team lead by Andrew Lowy at the Cancer Center and a current member of the CT2 Executive Committee. 

David Schlaepfer, PhD, Professor of Obstetrics, Gynecology and Reproductive Sciences. The Schlaepfer lab  has over 25 years of experience in studying FAK signaling and has participated in small molecule inhibitor  development as anti-tumor agents. Research projects are investigating whether selective inhibition of FAK  activity within tumor cells, stromal ECs, or both, will affect ovarian carcinoma tumor progression using transgenic  and implantable syngeneic mouse tumor models. Via ongoing collaborations with companies developing FAK  inhibitors including Poniard, GSK and Verastam, he has established that targeting a common signaling protein  (FAK), activated within ovarian carcinoma tumor cells and stromal ECs, may be a highly efficacious strategy to  block ovarian tumor progression and metastasis. Dr. Schlaepfer has mentored prior CT2 trainees into both  academic faculty and biotech positions. He is currently involved in a clinical trial for FAK inhibitors at UCSD. 

Stephen Schoenberger, PhD, Professor of Medicine. Dr. Schoenberger is an immunobiologist who is  investigating the mechanism by which primary B and T cells induce a state of antigen-specific immune tolerance  in CTL and the extent to which their transformed counterparts (lymphoma and leukemia) utilize the same pathway  to purge the host repertoire of T cells capable of recognizing the numerous mutated antigens which arise as a  consequence of neoplastic transformation. He has developed an MHC-agnostic system to evaluate key  neoepitopes capable of activating the immune response; he collaborates with many other preceptors listed here  to evaluate immunologic changes occurring across different cancers. 

Andrew Sharabi, MD, PhD, Assistant Professor of Radiation Medicine and Applied Sciences. Dr. Sharabi is a  nationally recognized expert on the effects of radiation on the immune system and is the Principal Investigator  of investigator-initiated Phase I and Phase II clinical trials combining radiation therapy with immunotherapies. In  addition, Dr. Sharabi serves as Chair of the American Society for Radiation Oncology (ASTRO) Education  Committee for Immunotherapy and is an Advisory Board Member for the San Diego Center for Precision  Immunotherapy (SDCPI). Dr. Sharabi’s NIH R01 and U01 funded research laboratory at the Moores Cancer  Center focuses on development of novel immunotherapies and strategies to combine radiation with novel  targeted agents in head and neck cancer. Research samples from clinical trials and preclinical models are being  analyzed in Dr. Sharabi’s lab to identify predictors of response, mechanisms of resistance, and the next  generation of treatments for head and neck cancer patients. Dr. Sharabi is a new member of the CT2 faculty. 

Jason Sicklick, MD, Executive Vice Chair of Research and Professor of Surgery. Dr. Sicklick’s lab studies  gastrointestinal stromal tumors (GIST), an orphan disease with approximately 5,000-6,000 new cases in the US  annually. He has cultivated a regional, national, and international referral pattern based upon his research. The  increased volume of patients then allows for a greater interchange between translational work in the lab and  clinical care at the bedside. He has recently received NCI R01 funding to explore the commonalities and  differences across tyrosine kinase inhibitor (TKI)-treated and genomically diverse GIST cancer stem cells, which  represent a novel target for overcoming disease persistence and TKI- resistance. In addition, this is the premise  for his funded FDA R01 titled “Open-Label, Phase 2 Efficacy Study of Temozolomide (TMZ) In Advanced  Succinate Dehydrogenase (SDH)-Mutant/Deficient Gastrointestinal Stromal Tumor (GIST).” In alignment with  the UCSD School of Medicine’s mission, his laboratory and clinical practice are a “place where discoveries are  delivered – bringing breakthroughs from the research lab to patients’ bedsides.” 

Robert Signer, PhD, Assistant Professor of Medicine. The Signer laboratory investigates stem cells at the  interface of regenerative medicine and cancer biology. Stem cells reside in many of our tissues and organs  throughout life. These rare stem cells have the remarkable potential to regenerate many of the specialized cells  in our bodies after they are lost to normal wear and tear, injury and/or disease. Declines in stem cell function  can lead to the onset of degenerative diseases. Over-activation or hijacking of stem cell activity can lead to  uncontrolled growth and cancer. Dr. Signer’s laboratory focus on how cell-type specific differences in protein  homeostasis network configuration and function promote stem cell longevity, enhance tissue regeneration and  suppress the development of cancer. In the present application, we are developing and adapting genetic and  pharmacological tools to disrupt translational fidelity in acute myeloid leukemia stem cells. These interventions  have the potential to disrupt protein homeostasis and impair the growth, survival, and self-renewal as well as  enhance the immunogenicity of cancer stem cells. Dr. Signer is a new faculty member and recently accepted a  new trainee into his laboratory. 

Nicole Steinmetz, PhD, Professor of Nanoengineering. Dr. Steinmetz is developing immunotherapeutic and  prophylactic vaccine approaches to the treatment of cancer. Her lab recently demonstrated, that plant virus-like  particles induce a potent anti-tumor response when introduced into the tumor microenvironment after tumors  (breast, melanoma, colon, ovarian) are established. Her data indicate effective treatment of established tumors,  but most importantly the in-situ vaccination approach induces immune memory, protecting patients from  outgrowth of metastatic disease or recurrence. In ongoing studies, she has demonstrated treatment of  companion dogs with metastatic melanoma. Data indicate that the potent anti-tumor efficacy of the plant virus based therapeutic can be replicated in these patients; this is of high clinical relevance, because the canine model  has considerable applicability to human melanoma. In addition to the in-situ vaccination approaches, she has  also pursued the development of cancer vaccines by using the plant virus nanotechnology as a display and  delivery technology to present B and T cell epitopes. Lastly, toward combination therapy and theranostics, she  has made multifunctional nanoparticles for combined drug delivery and/or with integrated imaging moieties for  multimodal imaging of the nanoparticle or disease site. 

Dwayne Stupack, PhD, Associate Professor of Obstetrics, Gynecology, and Reproductive Sciences & CT2 MPI.  Dr. Stupack’s research investigates the mechanisms by which tumor cells survive, thrive and metastasize. He  trained initially in genetics, though his early work led from immunology to the tumor microenvironment and to  angiogenesis. Currently, a major focus is on ovarian cancer tumor cells themselves, as a core project in his lab  focuses on the use of genomics and bioinformatics to discover vulnerable pathways. A common theme across  all these studies has been cell adhesion, extravasation, and cell migration. From early studies demonstrating  integrin regulation with cell activation, to antagonism of integrins, to mapping molecular determinants mediating  survival in the vasculature and in tumor cells, the work has contributed broadly to understanding cell signaling  pathways. Dr. Stupack has been involved in the early development of cell adhesion-targeted agents that have  reached late clinical trials (including the integrin antagonist cilengitide and the FAK inhibitor VS4718), and he continues to focus on the regulation of cell signaling processes dependent on cell adhesion receptors as well as  associated vulnerabilities identified via genomics. Dr. Stupack’s longstanding leadership within the CT2 and the  success of his past mentees led to his selection as renewal MPI. 

Pablo Tamayo, PhD, Professor of Medicine. The systematic sequencing of the cancer genome has provided a  powerful framework to identify genetic alterations in cancer. However, a deeper understanding of the functional  consequences of these alterations is necessary to develop more effective therapeutic strategies. Dr. Tamayo  has formulated a rational systematic approach to define and characterize oncogenic states and their most salient  genomic and immune hallmarks in order to infer optimal combinations of pharmacologic and immunological  perturbagens that disrupt their cancer cell and tumor microenvironment interaction and viability. The studies  from his laboratory have tested the hypothesis that in each identifiable oncogenic state there is a close interplay  between activation of oncogenic elements, cellular pathways, and the immune microenvironment. Dr. Tamayo  mentored a recent CT2 trainee into an academic leadership position. 

Judith Varner, PhD, Professor of Pathology. Dr. Varner is a well-known immuno-oncologist. She has discovered essential roles for integrins α4β1 and CD11b, PI3Kγ, Bruton’s Tyrosine Kinase, Kit and their  downstream effectors in tumor inflammation and progression. Together, these molecules regulate the  recruitment, proliferation, and polarization of myeloid cells in solid tumors. Most importantly, inhibitors of these  molecules block tumor inflammation and/or repolarize tumor associated myeloid cells toward an immune  stimulatory phenotype that combines with checkpoint inhibitors to eradicate tumors and promote long-term survival in mice. On the basis of her research, several inhibitors, including IPI-549 from Infinity Pharmaceuticals,  Ibrutinib from Pharmacyclics, and acalabrutinib from Acerta Pharma have been tested in cancer and other clinical  trials at the Moores Cancer Center and elsewhere. Her research program will continue to elucidate the molecular  basis by which myeloid cells impact infectious diseases and cancer growth and spread. Dr. Varner identifies pathways that regulate tumor associated macrophage polarization and tumor progression via activation of signal  transduction, epigenetic modification, and transcription mechanisms. She is also defining the molecular  mechanisms by which macrophages control tumor stemness and progression. Her research goals are to identify  targetable mechanisms that will be widely applicable to boost T cell activation to improve cancer outcomes. 

Peter Wang, PhD, Professor of Engineering. Controlling protein functions using physical approaches and  chemical compounds to trigger allosteric conformational changes can be applied to manipulate protein functions  and control cellular behaviors. Dr. Wang’s lab studies a novel class of machinery molecules that can provide a  surveillance of the intracellular space, visualizing the spatiotemporal patterns of molecular events and  automatically triggering corresponding molecular actions to guide cellular functions. He has adopted a modular  assembly approach to develop these machinery molecules to rewire the signaling pathways in  monocytes/macrophages for cell-based imaging and immunotherapies. He is also interested in applying lights  and ultrasound to manipulate the molecular activation of genes and enzymes, which allow us to control the cellular functions of immune T cells with high precision in space and time for cancer therapeutics. These  approaches should highlight the translational power in bridging fundamental molecular engineering to clinical  medicine and cancer therapies. 

Jing Yang, PhD, Professor of Pharmacology and Pediatrics. Dr. Yang is a cell biologist interested in the role of  the TWIST transcription factor in cellular transformation and response to carcinogen exposure. The Yang lab’s  long-term research goal is to elucidate the molecular basis of tumor metastasis and to identify new targets for  anti-metastasis therapy. Her pioneer research demonstrates a critical role of the Epithelial-Mesenchymal  Transition (EMT) in tumor metastasis. Currently, her research focuses on the regulation of epithelial mesenchymal plasticity in cancer invasion and metastasis. She aims to uncover novel extracellular and  intracellular regulatory mechanisms that control EMT dynamics during invasion and metastasis. Another focus  of her lab is to determine the dynamic role of EMT in tumor metastasis and treatment resistance. She is currently using various mouse models, human breast tumor cells, and PDX models to study EMT plasticity in metastasis  dormancy and chemoresistance. Lastly, she studies invadopodia-mediated matrix degradation in tumor  metastasis. Her current research aims are to identify and characterize novel invadopodia proteins that regulate  matrix degradation and tumor metastasis.  

Maurizio Zanetti, PhD, Professor of Medicine. Dr. Zanetti’s laboratory investigates the immune system and  ways to manipulate the immune response in distinct but interrelated areas of investigations. These include fate  determination of memory T cells, the impact of endoplasmic reticulum (ER) stress and the ER stress response  and functional characteristics of immune cells, and modular genetic programming in cell-based vaccines.  Currently, the lab is investigating immunochemical and cellular immunology tools, together with molecular  biology and gene analysis techniques, to investigate the nature of selected aspects of the immune response  and, contextually, develop principle-based new ways to regulate the immune response against cancer and viral  pathogens. 

Dong-Er Zhang, PhD, Professor of Pharmacology. Dr. Zhang’s lab is interested in the molecular pathology of  cancer development, progression, and treatment. Her lab uses molecular biology, protein biochemistry, cell  biology, and mouse models to address questions related to blood cell differentiation, transformation, and innate  immune responses. They discovered the synergistic effect of transcription factors RUNX1 (AML1) and C/EBP  in regulation of the blood cell gene expression and lineage development. Furthermore, they generated cell and  mouse models to study transcription factors and RNA binding factors in development of human leukemia. From  a study of a leukemia fusion protein expressing mouse model, they discovered a novel gene USP18 (UBP43)  and identified USP18 as an enzyme for controlling an interesting type of posttranscriptional protein modification  - ISGylation. Current efforts are investigating molecular bases of t(8;21) leukemia development and potential  treatment, RUNX1 mutations in blood cell malignancies, protein ISGylation in cancer and immune responses,  and immunotherapy for leukemia. Her former PhD student completed his MD and is now a CT2 trainee in the  Signer Lab. 

Liangfang Zhang, PhD, Professor of Nanoengineering, Director of Chemical Engineering Program, and Co Director of Center for Nano-Immunoengineering. Prof. Zhang leads an active research program of creating  cutting-edge biomimetic nanotechnologies and exploiting them to study and solve complex biological problems  that are associated with human diseases. One major research goal is to overcome the various therapeutic  barriers in the treatment of chemoresitant cancer and antibiotic-resistant bacterial infection. His research also  seeks to understand the fundamental sciences at the interface of nanomedicine and biology. Overall, Dr.  Zhang’s research program covers a broad scope of multidisciplinary areas including chemical & biomolecular  engineering, materials science, chemistry, nanotechnology, biotechnology, and medicine.

REQUIREMENTS

• CREST
• Ethics Requirements
• Lecture Series

Project Plan

Within 90 days of appointment, CT² trainees will be required to submit a 5 page project plan, structured in the format of a standard R01 application to be reviewed by the Executive Committee which will serve as the basis for the Committee’s assessment of their progress and performance throughout your 2-year period of training.

Review

Trainees will be consistently evaluated throughout their appointment term. Formal reviews (in the form of a presentation as part of the Topics in Cancer Drug Development Lecture series) may be required at months 8 and 20.

Grant Writing

The ability to prepare a cogent and clearly written research proposal is essential to the trainee’s ability to assume a leadership position in cancer drug development in academia or industry. Within the first 18 months, trainees are required to prepare a mock NIH application which will is critiqued by an ad hoc group of faculty members, acting as a typical Study Section, and provide written feedback to the fellow.

Clinical Research Enhancement Through Supplemental Training (CREST)

The UC San Diego School of Medicine has established a specialized program to doctoral candidates, postdoctoral fellows and junior faculty pursuing a career in clinical or translational research.  Scholars in this program complete a series of courses offered in a modular format. The CT² training program cross-registers its trainees in the CREST program and requires that they complete 5 of the following:

Feedback from previous appointees has indicated the high value of Biostats courses I and II. As such, both of these courses are now required for all trainees. The Scientific Communication module focuses on grant writing, scientific writing and presentation skills, is not required but is highly recommended for all Trainees; Patient Oriented Research I and II are recommended for MD Trainees.

The full CREST curriculum is designed to be delivered over two years and is comprised of eight modules which cover the principles of epidemiology, biostatistics, patient-oriented research (two modules each), health services/outcomes research, and career development (one module each). Each course is designed to be given over one academic quarter and is comprised of 10 weekly, 2-hour periods of instruction which are given in the early evening. The format for instruction includes a combination of didactic lectures, group discussions and hands-on computer-based training. Once-a-week evening classes allow the scholars to focus on their primary research projects during the work week with minimal interruption.

Since trainees enter the program with a variety of different backgrounds, two tracks are offered through the CREST program. In Track I Trainees take only a subset of 5 of the courses; in Track 2, Trainees take the entire set of 10 courses and earn a Certificate in Clinical Research upon completion. A third option, which requires all 10 courses listed above, an applied quantitative analysis course, two electives and an independent project, results in a Masters degree in Clinical Research. Feedback from current trainees has revealed a strong interest pursuing the Masters degree. CT² trainees may elect to participate in either Track I, II/Certificate in Clinical Research or pursue the Masters Degree.

A detailed description of the CREST coursework is described below:

Courses And Seminar Topics Available Through The CREST Program

Ethics Requirement

Trainees are required to take a program-approved Ethics course offered during the Fall, Winter and Spring quarters through the Research Ethics Program. This course satisfies the NIH requirement for instruction in the responsible conduct of research. Topics include roles and responsibilities of researchers, data collection and ownership, issues relating to use of animal and human subjects, scientific and grant writing, code of ethics for authors, reviewers and editors, and conflict of interest.

Lectures Series

Principles of Cancer Drug Therapeutics Development. This required lecture series consists of 12 weekly lectures delivered by CT² and UC San Diego faculty members during the fall quarter.  These lectures are focused specifically on the necessary sequential steps in drug development.

A second lecture series, Topics in Cancer Drug Development, is a series of 10 monthly lectures given by leaders in cancer drug development from industry. The goal of this lecture series is to expose trainees to experts with a substantial track record dealing with the “real life” challenges of cancer drug development. The lecturers are typically the CEO, Director of Research or Medical Director from a company in the San Diego biomedical community, although experts from large pharmaceutical companies have participated actively in this lecture series as well. The outside speakers are invited to discuss the real life challenges they face in the development of a given target or novel therapeutic and thus give the fellows an opportunity to hear the story of the development of specific therapeutic agents.

For the combined Principles of Cancer Drug Therapeutics Development and Topics in Cancer Drug Development lecture schedules, see the “Lecture Schedule” tab.

In addition to the two required lecture series, all CT² trainees (both PhDs and MDs) have the opportunity to attend several additional seminar programs based at the Moores UC San Diego Cancer Center:

• Research rounds: Held every Friday afternoon at 3:30, post-doctoral fellows from throughout all of the Cancer Center’s Programs are invited to present their research in a forum that promotes discussion and provides feedback. The research rounds are well attended by mentors and faculty who run laboratories in the Cancer Center.

• A weekly seminar “Topics in Hematology-Oncology” in which the faculty and fellows of the Division of Hematology/Oncology present lectures at 7:00 – 8:00 AM on Friday mornings on the clinical use of cancer therapeutic agents and the management of various types of cancer. This is followed by two case presentations (8:00 – 9:00) and then a formal lecture on a research topic by one of the Cancer Center faculty members (9:00 – 10:00).

• A monthly “Cancer Center Director’s Lecture Series” in which national leaders in cancer research from throughout the country are invited to lecture on their research.

It is also expected that trainees will attend research seminars, Tumor Boards and journal clubs specific to their area of specialization. The major biomedical institutions in San Diego (UC Sam Diego, Salk Institute, Sanford-Burnham Institute, and Scripps Research Institute) publish a weekly list of all the seminars scheduled and this averages >25 for any given week between September and June. Many of these deal with cancer therapeutics.  Each of the cancer- related clinical services has a weekly Grand Rounds open to CT² trainees and there are numerous journal clubs that meet on a weekly or bi-monthly basis. There are variety of opportunities to participate in a large number of additional training activities covering an enormously wide range of relevant topics.

APPLICATION INFORMATION

The Cancer Therapeutics Training (CT²) Program is an NIH-funded training program in cancer therapeutic development. This program accepts both PhD and MD post-doctoral researchers.

Download CT² Application Form

If you are interested in applying, please contact Amy Spilkin PhD (aspilkin@health.ucsd.edu).

ELIGIBILITY

Citizenship Requirements

CT² applicants must be United States citizens, noncitizen nationals or have been lawfully admitted for permanent residence by the time of their appointment.

Non-citizen nationals are people, who, although not citizens of the United States, owe permanent allegiance to the United States. They are generally people born in outlying territories of the United States (e.g., American Samoa and Swains Island). Individuals who have been lawfully admitted for permanent residence must have a currently valid Alien Registration Receipt Card (I-551) or other legal verification of such status.

Sorry, but individuals on temporary or student visas are NOT eligible for CT² support.

Prior Ruth L. Kirschstein-NRSA support

The National Research Service Award (now known as Ruth L. Kirschstein National Research Service Award) provides for a maximum of 3 years of post-doctoral funding.  Since the CT2 program requires a two-year, NRSA-eligible commitment, eligibility for the program requires that you have had no more than 1 year of prior NRSA post-doctoral support,

Faculty Mentor

All CT² applicants must identify a faculty mentor prior to having their application reviewed by the Executive Committee.  Please contact the mentor in whose laboratory you wish to complete your research prior to submitting your application.  A letter from your mentor expressing interest in having you join his/her group is required to move your application forward.

Application Requirements

If you would like to be considered for a training position please identify a faculty mentor and submit the following to aspilkin@health.ucsd.edu:

1. Cancer Therapeutics Training Program Application (with faculty mentor identified)
2. Curriculum Vitae
3. A one-page personal statement describing your past research or medical experience, why you are interested in the program, and your future goals
4. Proof of Citizenship
5. 3 formal letters of recommendation (should be PDF version, on letterhead, with signature)
6. A letter from your chosen mentor (this can substitute for one of the letters of recommendation) 

Please send application and other materials via e-mail:

Further Information

For further information, please contact the CT² Program Manager, Amy Spilkin PhD, via email at aspilkin@health.ucsd.edu.

CONTACT INFORMATION

For all other inquiries, please e-mail: aspilkin@health.ucsd.edu

LECTURE SERIES

All lectures are on Tuesdays from 12 to 1 p.m. in Comer Commons at Moores Cancer Center (directions and map). Lunch is available at 11:45 a.m. for those attending the lecture.

Principles of Cancer Drug Therapeutics Development

This is a required series of 12 weekly lectures delivered by CT2 and UC San Diego faculty members during fall quarter. They focus on the necessary sequential steps in drug development.

Topics in Cancer Drug Development

This is a series of 10 monthly lectures by industry leaders in cancer drug development. The goal is to expose trainees to experts with a substantial track record in the “real life” challenges of cancer drug development. The lecturers are typically CEOs, directors of research, or medical directors from companies in the San Diego biomedical community, although experts from large pharmaceutical companies have also participated. The outside speakers are invited to discuss challenges of developing a given target or novel therapeutic and give fellows an opportunity to hear the story of the development of specific therapeutic agents.

Upcoming Lectures

Please visit the Events & Seminars page for more information.

• 2018-2019 Lecture Series
• 2017-2018 Lecture Series
• 2016-2017 Lecture Series
• 2015-2016 Lecture Series
• 2014-2015 Lecture Series
• 2013-14 Lecture Schedule
• 2012-13 Lecture Schedule
• 2011-12 Lecture Schedule
• 2010-11 Lecture Schedule
• 2009-10 Lecture Schedule