NIH T32 Training Program in Surgical Oncology Research at Penn
The Department of Surgery at the University of Pennsylvania Perelman School of Medicine has established a T32 Training Program in Surgical Oncology Research that is funded by the National Cancer Institute. The program supports surgical residents who will conduct two years of full-time research in basic, translational, or clinical (e.g. health services research, disparities, and clinical trials) research focusing on cancer-related topics. The trainee will work directly with an NIH-funded mentor of their choosing at the University of Pennsylvania. The program includes a robust educational component. There are multiple opportunities to obtain a Master’s degree, such as in health policy research, epidemiology, biostatistics, or translational research. A two-year commitment is mandatory.
We seek candidates who embrace and reflect diversity in the broadest sense. The University of Pennsylvania is an Equal Opportunity Employer.
There are three new positions for each academic year starting July 2021.
Program Goals and Activities
The goal of the T32 program is to train surgeon-scientists in the scientific method in order to make meaningful contributions to cancer research during their academic career. Trainees will participate in didactics, seminars, and journal clubs and complete a course in the Responsible Conduct of Research (RCR). The T32 trainee will not have clinical responsibilities.
- Resident in good standing in an ACGME-approved surgery training program within the United States. Typically, the resident will have completed 2-3 years of clinical, surgical training.
- Ability to perform 2 consecutive years of full-time research.
- U.S. citizen or permanent resident as per NIH stipulations.
- The applicant may not have already received >1 year of support from another T32 or an individual NIH award.
Program Mentors -
Steven Albelda, MD - My research interests focus on developing novel approaches to the treatment of mesothelioma, lung cancers, and other thoracic malignancies. My clinical interests are primarily in thoracic oncology. In 1992, I founded a translational “Thoracic Oncology Research Laboratory” aimed at moving research from “bench to bedside”. I have led an NCI-funded Program Project aimed at developing new treatments for mesothelioma for the past 22 years. The major areas of recent interest in the lab have been augmentation of anti-tumor immune effects, the tumor microenvironment, mechanisms of T cell dysfunction, and adoptive T cell transfer. To study these, my lab has developed a wide variety of animal models of lung cancer and mesothelioma that can be used to evaluate new therapies and T cell function. We have also analyzed human samples from many clinical trials. The lab has extensive experience in lentiviral transduction of human T cells and retroviral transduction of mouse T cells for use in adoptive T cell transfer.
I am committed to post-doctoral training since I have trained more than 70 post-doctoral fellows. With respect to this application I can provide training in the following broad areas that are associated with tumor immunology including he tumor microenvironment, lung cancer and mesothelioma biology and carcinogenesis. Having mentored on a T32 for the last 20 years of my career, I understand the commitment and the path to success for these trainees.
- Singhal S, Standanlick J, Annunziata M, Rao A, Bhojjagarwala P, O’Brien S, Moon EK, Cantu E, Danet-Desnoyers G, Ra H-J, Litzky L, Akimova T, Beier UH, Hancock, Albelda SM, Eruslanov EB. Human tumor-associated monocytes/macrophages and their regulation of the tumor-specific effector Tcell responses in early-stage lung cancer: role of macrophage- versus tumor-expressed PD-L1. Science Translational Med, 2018, 13:11(479)
- O’Brien SM, Klampatsa A, Thompson JC, Martinez MC, Hwang WT, Rao AS, Standalick JE, Kim S, Cantu E, Litzky LA, Singhal S, Eruslanov E, Moon EK, Albelda SM. Function of Human Tumor-Infiltrating Lymphocytes in Early Stage Non-Small Cell Lung Cancer. Cancer Immunology Research, 2019 7:896-909. PMID 31053597.
- Wang E, Wang LC, Tsai CY, Gershenson Z, Moon E, Newick K, Sun J, Lo A, Baradet T, Feldman MD, Barrett D, Pure E, Albelda S, Milone MC. Generation of potent T-cell immunotherapy for cancer using DAP12-based, multichain, chimeric immunoreceptors. Cancer Immunol Res. 3:815-26. 2015. PMCID: PMC25941351.
- Newick K, O’Brien S, Sun J, Kapoor V, Maceyko S, Lo A, Pure E, Moon E, Albelda SM. Augmentation of CAR T cell trafficking and antitumor efficacy by blocking protein kinase A (PKA) localization. Cancer Immunology Research, 6:541-51, 2016 PMCID: PMC4891259
Edward Delikatny, PhD -
I have over 25 years experience in molecular imaging in tumor cells and animal models especially with regard to alterations in lipid metabolism associated with apoptotic cell death due to anticancer drugs. Much of our recent research is based on the development of near-infrared fluorescent contrast agents for detection of metabolism in vivo and for surgical margin detection. We have synthesized molecular imaging probes for detection of tumor microenvironment pH using Cerenkov imaging, activatable probes for detection of phospholipases and probes for detection of choline kinase. The choline kinase sensors are based on a unique
design in which a NIR fluorophore is modified to contain a choline mimetic group that interacts directly with the enzyme active site and functions as a competitive inhibitor. We have shown that these probes can report on the level of choline kinase expression in breast tumor models and can monitor the response to anticancer therapy in vivo. For purposes of this T32 training grant, I have been working with surgeons for the last 5 years and have multiple joint publications with Dr. Sunil Singhal (Associate Program Director of the proposal and with Dr. David Holt, a veterinary oncology surgeon from the School of Veterinary Medicine. I have worked closely with surgical residents (Jarrod Predina, Andrew Newton) over the last 3 years so I feel comfortable training future residents.
I am committed to diversity training and have mentored 10 underrepresented candidates, two current graduate students, one who successfully defended his Ph.D. thesis in Aug. 2019, one postdoc who is now an Associate Professor in Radiology at UTSW; a research technician who is in his final year of the MD/PhD program at the University of Rochester, and six undergraduate students in Penn’s Summer Undergraduate Internship (SUIP) program. Three of my SUIP students entered graduate school at Penn and one at Harvard. One of these recently defended her thesis and is now doing postdoctoral studies. One SUIP student has completed medical school, and the sixth is employed at the Broad Institute of MIT and Harvard.
- Arlauckas, S.P., Kumar, M., Popov, A.V., Poptani, H. and Delikatny, E.J. (2017). Near infrared fluorescent imaging of choline kinase alpha expression and inhibition in breast tumors. Oncotarget 8, 16518-16530.
- Arlauckas, S.P., Popov, A.V. and Delikatny, E.J. (2016). Choline kinase alpha - Putting the ChoK-hold on tumor metabolism. Prog Lipid Res. 63, 28-40. PMCID: PMC5360181
- Judy, R., Keating, J., DeJesus, E., Jiang, J., Okusanya, O., Nie, S., Holt, D., Arlauckas, S., Low, P., Delikatny, E.J. and Singhal, S. (2015). Quantification of tumor fluorescence during Intraoperative optical cancer imaging. Scientific Reports. 5, 16208. PMCID: PMC4643322
- Keating, J., Newton, A., Venegas, O., Nims, S., Zeh, R., Predina, J., Deshpande, C., Kucharczuk, J., Nie, S., Delikatny, E.J., Singhal, S. (2017). Near-Infrared intraoperative molecular imaging can locate metastases to the lung. Ann. Thorac. Surg. 103: 390-398.
Ronald DeMatteo, MD (Program Principal Investigator) - I am the Program Director of the proposed T32 Surgical Oncology Research Training Program. I became the Chair of Surgery at the Perelman School of Medicine at the University of Pennsylvania two years ago. I am a physician scientist who was appointed to the staff at Memorial Sloan Kettering Cancer Center in 1999. There, I was the Vice Chair of the Department of Surgery from 2006-17 and had a Joint Appointment in the Immunology Program of Sloan Kettering Institute. I was the Program Director of the clinical Surgical Oncology fellowship for 7 years and have mentored over 100 fellows. I won a departmental teaching award in 2017. In my laboratory, I have trained over 30 surgery residents. Furthermore, I was the Associate Program Director of the T32 in Surgical Oncology at Memorial Sloan Kettering from 2006-12, and then became the Principal Investigator for the competitive renewal that covered the period 2012-17.
I specialize in the treatment of hepatopancreatobiliary cancers and gastrointestinal stromal tumor (GIST). While I have performed research in liver immunology and inflammation, my primary focus has been on the molecular, immunologic, and clinical aspects of gastrointestinal stromal tumor (GIST). GIST is the most common type of sarcoma and it arises from the gastrointestinal tract. We have created a large collaborative team involving a sarcoma pathologist, molecular biologist, bioinformatics expert, and medical oncologists. We have developed several genetically engineered mouse models of GIST and have routine access to fresh human GIST surgical specimens from consenting patients. We have translated several of our laboratory findings into clinical trials. A CTEP Phase I trial of dasatinib and ipilimumab for advanced GIST has been completed.
Unexpectedly, we discovered that part of the efficacy of imatinib in GIST depended on inhibition of indoleamine 2,3-dioxygenase (IDO), an immunosuppressive protein made by many tumors. We found that imatinib and the immune agent anti-CTLA-4 were synergistic in a genetically engineered mouse model. Furthermore, to our knowledge, we were the first group to freshly isolate intratumoral macrophages from a human cancer and subject them to detailed phenotypic, molecular, and functional analyses. We determined that intratumoral macrophages in human GISTs were highly dynamic as they were actually anti-tumoral at baseline, became pro-tumoral after imatinib therapy, and reverted to anti-tumoral upon imatinib resistance. The mechanism was mediated by C/EBP transcription factors and the findings have implications for the clinical application of macrophage-directed therapy. Recently, we found that the immune response to GIST depends on the driver mutation. In addition, imatinib inhibits intratumoral dendritic cell development, resulting in less active anti-tumoral T cells.
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- Cavnar MJ, Zeng S, Kim TS, Sorenson EC, Ocuin LM, Balachandran VP, Seifert AM, Greer JB, Popow R, Crawley MH, Cohen NA, Green BL, Rossi F, Besmer P, Antonescu CR, DeMatteo RP. KIT oncogene inhibition drives intratumoral macrophage M2 polarization. J Exp Med 2013; 210:2873-86. PMCID: PMC3865475
- Vitiello GA*, Bowler TG*, Liu M, Medina BD, Zhang JQ, Param NJ, Loo JK, Goldfeder RL, Chibon F, Rossi F, Zeng S, DeMatteo RP. Differential immune profiles distinguish the mutational subtypes of gastrointestinal stromal tumor. J Clin Invest 2019. Epub. PMID30762585
- Medina BD, Vitiello GA, Seifert AM, Zeng S, Liu M, Bowler T, Zhang JQ, Cavnar MJ, Loo JK, Param NJ, Maltbaek JH, Rossi F, Balachandran VP, DeMatteo RP. Oncogenic kinase inhibition limits Batf3-dependent dendritic cell development and anti-tumor immunity. J Exp Med 2019. Epub. PMID:31000683
Evgeniy Eruslanov, PhD - For the last decade, I have been studying tumor immunology. Specifically, I have been investigating the role of inflammatory myeloid cells in the tumor microenvironment and mechanisms by which tumors modulate their immune functions. My ultimate research goal is to develop novel approaches that will enhance endogenous immune response in order to break tumor-induced tolerance/suppression and to improve the efficacy of immunotherapy for lung cancer. I have been working with surgeons and surgical residents for over one decade, so I am delighted to act as a mentor for future surgical oncology residents as part of this T32 training grant. Although I have not trained surgical residents, my master’s and PhD trainees have been hired at top universities such as Harvard and UPenn.
- Singhal S, Stadanlick J, Annunziata MJ, Rao AS, Bhojnagarwala PS, O'Brien S, Moon EK, Cantu E, Danet-Desnoyers G, Ra HJ, Litzky L, Akimova T, Beier UH, Hancock WW, Albelda SM, Eruslanov E. Human tumor-associated monocytes/macrophages and their regulation of T cell responses in early-stage lung cancer. Science Translational Medicine. 2019, Feb 13; 11(479).
- Singhal S, Bhojnagarwala P, O’Brien S, Moon E, Garfall A, Rao A,. Quatromoni J, Stephen T, Litzky L, Deshpande D, FeldmanM, HancockW, Conejo-Garcia J, Albelda S, and Eruslanov E. Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen Presenting Cell Features in Early-Stage Human Lung Cancer. Cancer Cell, 2016, Jun 30.
- Eruslanov E, Bhojnagarwala P, Quatromoni J, Stephen T, Ranganathan A, Deshpande C, Akimova T, Vachani A, Litzky L, Hancock W, Conejo-Garcia J, Feldman M, Albelda S, and Singhal S. Tumorassociated neutrophils stimulate T cell responses in early-stage human lung cancer. The Journal of Clinical Investigation, 2014, Dec 1; 124(12): 5466-80.
- Eruslanov E, Stoffs T, Kim W, Daurkin I, Gilbert S, Su LM, Vieweg J, Daaka Y, and Kusmartsev S. Expansion of CCR8+ inflammatory myeloid cells in cancer patients with urothelial and renal carcinomas. Clinical Cancer Research. 2013, Apr 1; 19(7): 1670-80.
Malay Haldar, MD, PhD - My laboratory studies how tumor microenvironment regulates the differentiation and function of innate immune
cells of the mononuclear phagocyte system (MP cells), which comprises of monocytes, dendritic cells (DC), and macrophages. MP cells perform diverse function; from controlling immune responses to maintaining tissue homeostasis. This functional diversity is reflected in their phenotypic and developmental heterogeneity. Tissueassociated factors are thought to control the influx, differentiation, and function of MP cell subsets, which is underscored by their dramatic redistribution in tissues under various pathological states. Our laboratory is interested in: (1) how tumor-associated MP cells contribute to tissue homeostasis and pathological states and (2) pathways controlling the development of distinct tumor-associated MP cell subsets. In the context of human diseases, we are particularly interested in solid tumors. Tumor-infiltrating MP cells can shape the immunosuppressive tumor microenvironment, which is a major barrier to immunotherapy. We are investigating the bi-directional cross-talk between tumor microenvironment and MP cells that generates this immunosuppressive milieu with the overarching goal of targeting these cells for immunotherapy. In our approach, we integrate data from genetically engineered mouse models, patient-derived samples, basic molecular biology, and high dimensional immune and genomic profiling to generate and test hypothesis.
I have been training residents for the last 4 years, and in fact, currently have a surgical resident in my laboratory who is pursuing his PhD. I am confident that I can prepare surgeons to be the highest caliber academic Surgical Oncologists for the coming decades.
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Gerald Linette, MD, PhD - My primary interest is human cancer immunology. My graduate studies concentrated on HIV-1 immunobiology. Since 1996, I have been actively involved in the development of new therapeutic approaches for melanoma, including dendritic cell vaccines, gene therapy, adoptive T cell therapy, and checkpoint inhibitors. My laboratory research is comprised of various trainees including clinical fellows, post-doctoral fellows, graduate students, undergraduates as well as senior research investigators with specialization in molecular biology and cellular immunology. We are a member of the Center for Cellular Immunotherapies and the Parker Institute for Cancer Immunotherapy at Penn. As part of a larger clinical multidisciplinary effort, I serve as the principle investigator for consortium and investigator-initiated clinical trials. My current research focus is the identification of MHC class I restricted neoantigens encoded by various malignancies and implementation of new cell therapy approaches for melanoma and other solid tumors. Our group employs next generation sequencing technologies through active collaborations with experts in genomics, proteomics, and bioinformatics. Given my extensive experience with training fellows and residents, I would be honored to train Surgical Oncologist as part of the T32 Training Grant in Surgical Oncology proposed by the Department of Surgery and Dr. Ron DeMatteo.
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- Migliorini D, Dietrich PY, Stupp R, Linette GP, Posey AD, June CH. CAR T cell therapies in glioblastoma: a first look. Clin Cancer Res. 2017 Nov 20. pii: clincanres.2871.2017. doi: 10.1158/1078-0432.CCR-17-2871. PMID: 29158268.
Sunil Singhal, MD (Track Leader) - The fundamental question of my research is: “After a curative cancer surgery, why do some patients still develop recurrences?” I hypothesize patients who undergo surgery develop relapses for two fundamental reasons: (i) micrometastatic disease in the local wound bed, and (ii) failures in the host immune system that prevent systemic disease. Furthermore, I postulate that the optimal time to cure cancer patients is during the time of surgery because they have the least quantity of residual disease. To study this hypothesis, I have developed two simultaneous research efforts. Over the last 10 years, I have built both research programs. I have NIH funding to support both programs, and my mixed bibliography will attest to these efforts. First, I study methods of molecular imaging “intraoperative molecular imaging”) to identify residual tumor cells in the wound bed after surgery. Ultimately, if surgeons can perform a better surgery, the likelihood of a local recurrence and an inadequate staging should diminish. Second, I have pursued a more detailed examination of the immune factors that exist at the time of surgery, and why these factors fail to prevent systemic relapses despite minimal residual disease. If these perioperative immune elements can be mapped, then the use of tumor immunotherapy during this golden period of reduced tumor burden may be a solution to prevent systemic recurrences.
- Predina JD, Eruslanov E, Judy B, Kapoor V, Cheng GJ, Wang S, Sun J, Fridlender G, Albelda SM, Singhal S. “Changes in the Local Tumor Microenvironment in Recurrent Cancers May Explain the Failure of Vaccines after Surgery.” Proceedings of the National Academy of Sciences. 110(5): E415-24. Jan 29, 2013. PMCID: PMC3562776.
- Eruslanov E, Bhojnagarwala PS, Quatromoni JG, Stephen TL, Ranganathan A, Deshpande C, Akimova T, Vachani A, Litzky L, Hancock WW, Conejo-Garcia JR, Feldman M, Albelda SM, Singhal S. “Inflammatory Tumor-associated Neutrophils in Early Stage Human Lung Cancer.” Journal of Clinical Investigation. 124(12):5466-80. December 1, 2014. PMCID: PMC4348966.
- Singhal S, Bhojnagarwala PS, O’Brien S, Moon EK, Garfall AL, Rao A, Quatromoni JG, Stephen TL, Litzky L, Deshpande C, Feldman M, Hancock WW, Conejo-Garcia JR, Albelda SM, Eruslanov EB. “Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen Presenting Cell Features (Hybrid TANs) in Early-Stage Human Lung Cancer.” Cancer Cell. 2016. PMCID: PMC4945447w
- Singhal S, Stadanlick J, Annunziata MJ, Rao AS, Bhojnagarwala PS, O’Brien S, Moon EK, Cantu E, Danet-Desnoyers G, Ra HJ, Litzky L, Akimova T, Beier UH, Hancock WW, Albelda SM, Eruslanov EB. “Human tumor-associated monocytes/macrophages and their regulation of the tumor-specific effector T cell responses in early-stage lung cancer: role of macrophage- versus tumor-expressed PD-L1.” Science Translational Medicine. (11) 479, 2019.
Robert Vonderheide, MD, DPhil - I am the Director of the Abramson Cancer Center and the John H. Glick, MD Abramson Cancer Center’s Director Professor at the University of Pennsylvania. I am considered an international leader in pancreatic cancer immunobiology. I co-lead a SU2C Team on Pancreatic Cancer Immunotherapy. My laboratory combines efforts in both basic research and clinical investigation to advance the understanding of tumor immunology and to develop novel immunotherapies for cancer. The basic research focus in my laboratory includes deciphering the immunobiology of novel genetically engineered mouse models of cancer, including the regulation of immune surveillance and the tumor microenvironment by CD40. My translational work tests novel approaches such as vaccines, antibodies, and adoptive T cells for the treatment of patients with pancreatic cancer, breast cancer and melanoma. I have also studied ‘universal’ tumor antigens such as hTERT and immune modulatory pathways involving CD40, GM-CSF, CXCR2, PD-1, CTLA-4, and CD25.
I have a significant experience in training residents, and I have trained over 50 postdocs in my career. A large portion of them are in academic positions with their own NIH grants. Therefore, I am confident that if a surgical resident chooses my lab, they will be well prepared to do rigorous scientific research in their own careers.
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Program Mentors -
Rinad Beidas, PhD - I am an implementation scientist and the Founder and Director of the Penn Implementation Science Center at the Leonard Davis Institute (PISCE@LDI) at the University of Pennsylvania. My research focuses on advancing the study of methods to promote the systematic uptake of evidence-based practices into routine clinical care to improve the quality and effectiveness of health and behavioral health services (i.e., implementation science). Specifically, my interests relate to the measurement of implementation outcomes (e.g., fidelity; R01 MH108551), designing and testing implementation strategies using systematic and rigorous methods with an eye towards targets and mechanisms (e.g., R21 MH 109878; AHRQ R13HS025632), and collaborating with community stakeholders to understand the best ways to implement evidence-based practices and improve services across a variety of settings. I have been identified as one of the top ten implementation scientists nationally (Norton et al., 2017) and have published over 100 articles in this area. I co-lead an NIH Center on behavioral economics, implementation science, and mental health (P50 MH 113840) and have a strong record of NIH-funded implementation research (I have served as MPI or PI of six NIH grants totaling over $10 million and serve as a co-investigator on grants from NCI, NHLBI, and NIMH). I also have a history of mentoring postdoctoral fellows (I am MPI of a T32 on implementation science from NIMH) and junior faculty (including those on K awards from NCI), and of building implementation science capacity at Penn through PISCE@LDI. I serve as an ad hoc study section member of the Dissemination and Implementation Research in Health committee and as 2019 faculty for the Training Institute in Dissemination and Implementation in Cancer (TIDIRC). These experiences makes me an ideal mentor for this T32. As MPI of a T32 from NIMH, I have mentored a number of pre- and post-doctoral trainees as over the past 7 years, making me well suited for this role. With respect to this application, I can provide training in implementation science, which is an important topic for surgical oncology.The following manuscripts highlight my extensive experience conducting implementation trials.
- Williams NJ, & Beidas RS. Annual Research Review: The state of implementation science in child psychology and psychiatry: a review and suggestions to advance the field. Journal of Child Psychology and Psychiatry. Epub 2018.
- Beidas RS, Marcus S, Aarons GA, Hoagwood K, Schoenwald S, Evans A, Mandell DS. Individual and organizational factors related to community clinicians’ use of therapy techniques in a large public mental health system. JAMA Pediatrics. 2015;169:374-82. PMCID: PMC4420189
- Beidas RS, Paciotti B, Barg F, Branas A, Brown J, Glanz K, Schmitz K. A hybrid effectiveness-implementation trial of an evidence-based exercise intervention for breast cancer survivors. Journal of the National Cancer Institute Monographs. 2014;338-45. PMCID: PMC4411538.
- Beidas RS, Kendall PC. Dissemination and implementation of evidence-based practices in child and adolescent mental health. Oxford University Press; 2014.
Justin Bekelman, MD - I am a practicing radiation oncologist and physician-scientist with expertise in clinical epidemiology and health services research. My research programs focus on two themes: cancer comparative effectiveness and delivery system and payment reform, integrating methods from the fields of epidemiology, clinical trials, health economics and public policy. In cancer comparative effectiveness research, my research employs several methodological approaches to conduct randomized and non-randomized studies addressing important evidence gaps in cancer care. My research group has also developed and applied tools to mitigate the limitations of non-randomized studies of cancer interventions, using traditional regression, instrumental variable, and causal inference methods. I am the PI of a large-budget R01-level multi-center pragmatic randomized clinical trial comparing proton to photon radiation therapy for breast cancer enrolling at over 60 US treatment centers and funded by the Patient-Centered Outcomes Research Institute. In delivery system and payment reform research, I conduct observational, quasi-experimental and randomized studies to identify and characterize low-value cancer care and to develop and evaluate interventions to promote high-value cancer care, with a particular emphasis on how financial and non-financial incentives affect provider behavior. In summary, my expertise, skills, experience, and supportive environment have prepared me to successfully serve as XXXX on this proposed research.
- Bekelman JE, Sylwestrzak G, Barron J, Liu J, Epstein AJ, Freedman G, Malin J, Emanuel EJ. Uptake and Costs of Hypofractionated vs. Conventional Whole Breast Irradiation After Breast Conserving Surgery in the United States, 2008 – 2013. JAMA. 2014 Dec 17;312(23):2542-50. PMID: 25494006.
- Bekelman JE, Halpern SD, Blankart CR, Bynum JP, Cohen J, Fowler R, Kaasa S, Kwietniewski L, Melberg HO, Onwuteaka-Philipsen B, Oosterveld-Vlug M, Pring A, Schreyögg J, Ulrich CM, Verne J, Wunsch H, Emanuel EJ. Comparison of Site of Death, Health Care Utilization, and Hospital Expenditures for Patients Dying With Cancer in 7 Developed Countries. JAMA. 2016 Jan 19;315(3):272-283. PMID: 26784775.
- Ojerholm E, Halpern SD, Bekelman JE. Default options: opportunities to improve quality and value in oncology. J Clin Oncol. 2016 34(16):1844-71847.
- Bekelman JE and Joffe S. Three Steps Toward a More Sustainable Path for Targeted Cancer Drugs. JAMA. 2018 Jun 5;319(21):2167-2168.
Angela Bradbury, MD - As a medical oncologist with specialized training in clinical cancer genetics, cancer prevention, and medical ethics, I have been developing and leading translational genetic research focused on the clinical implementation of genetic medicine to promote the health of individuals, families, and communities since 2003. This includes research evaluating novel delivery models to facilitate dissemination and implementation of cancer genetics and evaluation of the psychosocial and behavioral outcomes of genetic testing (R01 CA160847-01A1 and R21CA164121-02), studies evaluating the outcomes with return of multiplex genetic research results for breast cancer susceptibility (ACRA 2013, R01 CA190871) and the impact of genetic and familial risk on children, adolescents, and families (R01 CA138819 Daly/Bradbury, Basser Center for BRCA1/2 Research). Many of these studies have incorporated eHealth approaches to delivery of genetic services for cancer and Alzheimer’s disease, including telephone and videoconferencing delivery (R01 CA160847 and R21CA164121-02, UF1AG046150), as well as Internet Genetic Education Delivery to facilitate informed decision-making regarding receipt of individual genetic research results (R01 CA190871, COMET ancillary study to MATCH). Each of these studies or subprojects has been under my leadership. Equally important, I have been providing clinical care to individuals at high risk for cancer and patients receiving cancer genetics services for over 10 years. Thus, my experience as an independent physician-scientist, ongoing research program and strong collaborative relationships provide the experience and expertise to lead the proposed research.
- Patrick-Miller L, Egleston B, Daly MB, Stevens E, Fetzer D, Forman A, Bealin L, Rybak C, Peterson C, Corbman M, Bradbury AR. Implementation and outcomes of telephone disclosure of clinical BRCA1/2 test results. Patient Education and Counseling. 2013 Dec;93(3):413-9. PMID: 24075727. PMCID:PMC4199583.
- Bradbury AR, Patrick-Miller L, Long J, Powers J, Stopfer J, Forman A, Rybak C, Mattie K, Brandt A, Chambers R, Chung WK, Churpek J, Daly MB, Digiovanni LD, Farengo-Clark D, Fetzer D, Ganschow P, Grana G, Gulden C, Hall M, Kohler L, Maxwell K, Merrill S, Montgomery S, Mueller R, Nielsen S, Olopade O, Rainey K, Seelaus C, Nathanson KL, Domchek SA. Development of a Tiered and Binned Genetic Counseling Model for Informed Consent in the Era of Multiplex Testing for Cancer Susceptibility. Genetics in Medicine 2015, 17(6):485-92. PMID: 25297947. PMCID: PMC4983405.
- Bradbury AR, Olopade OI, Dignam JJ, Ibe CN, Auh SL, Hlubocky FJ, Cummings SA, White MA, Daugherty CK. How often do mutation carriers tell their young children of the family’s risk for cancer? A study of parental disclosure of BRCA mutations to minors and young adults. Journal of Clinical Oncology 25 (24): 3705-11, 2007. PMID:17704419.
- Terry MB, Bradbury AR. Family-based Breast Cancer Prevention Efforts in Adolescence. Pediatrics 2016 Nov: 138 (Suppl 1):S78-S80.PMID: 27940980.
Angela DeMichele, MD, MSCE - I am a breast cancer oncologist, trialist and clinical epidemiologist. My research focuses on the development of investigational therapeutics, identifying biomarkers predictive of outcome/response to therapy and development of novel approaches to treat minimal residual disease to prevent recurrence. Nationally, I Co-Chair the ECOG/ACRIN Cooperative Group Breast Committee, am a PI in the Translational Breast Cancer Research Consortium and Chair the Trial Operations Working Group of the I-SPY2 Trial. I am the PI of numerous investigator-initiated clinical trials and translational epidemiologic studies, including nternational Co-PI of the PALLAS Adjuvant Palbociclib Trial). At the University of Pennsylvania Abramson Cancer Center, I Co-Direct the 2-PREVENT Translational Center of Excellence, and Co-Lead the ACC Breast Cancer Program. In these roles, I have built a multidisciplinary, peer-review funded research program and developed translational resources, including a comprehensive biobank and database. In addition, I have trained the next generation of clinical researchers through individual mentorship in Masters in Clinical Epidemiology and development of the Clinical Trials course in the Center for Clinical Epidemiology, Biostatistics and Bioinformatics. My experience and expertise in all aspects of drug and biomarker development and clinical trial design and conduct are especially well suited to developing and implementing the research proposed in this application.
- Rugo HS, Olopade OI, DeMichele A, Yau C, van 't Veer LJ, Buxton MB, Hogarth M, Hylton NM, Paoloni M, Perlmutter J, Symmans WF, Yee D, Chien AJ, Wallace AM, Kaplan HG, Boughey JC, Haddad TC, Albain KS, Liu MC, Isaacs C, Khan QJ, Lang JE, Viscusi RK, Pusztai L, Moulder SL, Chui SY, Kemmer KA, Elias AD, Edmiston KK, Euhus DM, Haley BB, Nanda R, Northfelt DW, Tripathy D, Wood WC, Ewing C, Schwab R, Lyandres J, Davis SE, Hirst GL, Sanil A, Berry DA, Esserman LJ; I-SPY 2 Investigators. (2016). Adaptive Randomization of Verliparib-Carboplatin Treatment in Breast Cancer. N Engl J Med. 375(1):23-34. PMID:27406347
- DeMichele A, Clark AS, Kay S Tan KS, Daniel F Heitjan DF, Kristi Gramlich K, Gallagher M, Lal P, Feldman M, Zhang P, Colameco C, Lewis D, Langer M, Goodman N, Domchek SM, Gogineni K, Rosen M, Fox KR, and O'Dwyer P. (2015). CDK 4/6 Inhibitor Palbociclib (PD0332991) in Rb+ Advanced Breast Cancer: Phase II Activity, Safety and Predictive Biomarker Assessment Clin Cancer Res. 21(5):995-1001. PMID: 25501126
- Mao JJ, Su HI, Feng R, Donelson ML, Aplenc R, Rebbeck TR, Stanczyk F, and DeMichele A. (2011) Association of functional polymorphisms in CYP19A1 with aromatase inhibitor associated arthralgia in breast cancer survivors. Breast Cancer Res 13(1): R8. PMCID: PMC3109575.
- DeMichele A, Martin A, Mick R, Wray L, Cabral M, Athanasiadis G, Colligan T, Stadtmauer E and Weber B. (2003) Interleukin-6 (IL-6)-174G>C Polymorphism is Associated with Improved Outcome in High Risk Breast Cancer. Cancer Res 63:8051-56.
Rachel Kelz, MD, MSCE (Track Leader) - I am a board-certified general surgeon with formal training in health services research and business. My clinical practice is focused on endocrine and oncologic surgery. Within the Department of Surgery (DOS), I serve as the Vice Chair for Clinical Research and the Founding Director of the Center for Surgery and Health Economics. I am committed to improving surgical quality and eradicating disparities in cancer care through innovative education and scientific investigation. I devoted much of my first seven years on faculty at PENN to education. I was recognized for my contributions to the educational programs with the Gordon P. Buzby Award for Leadership and the Christian R. and the Mary F. Lindback Award for Distinguished Teaching, the most prominent educational award given by the University. More recently, I have focused on multidisciplinary, collaborative research as a mechanism to improve surgical care delivery and outcomes for patients with benign and malignant diseases. As an R01 funded investigator, I am working to establish standards in surgical education and advance health services organization and delivery to improve surgical cancer care. I am a senior scholar at the Leonard Davis Institute. I serve as the Secretary (Executive Board Member) of the Society of Clinical Surgery, a Councilor-at-Large (Executive Council) for the Society of University Surgeons, a Member of the Board of Directors of the Surgical Outcomes Club, and as the Director of the American College of Surgeons National Quality In-Training Initiative. My role as a leader in Surgery, Education, and Health Services Research will facilitate the training of future surgeon-scientists in surgical oncology, and provide a national network for their future growth and development. As witnessed by the successes of my mentees, and recognition from the DOS as a Mentorship Awardee (2014), I have made mentoring junior investigators a priority. As a surgeon-scientist with collaborations across disciplines and universities, and an established track record of mentoring young investigators, I am fully committed to and capable of supporting the training opportunities put forth in the T32 proposal entitled, “Surgical Oncology Research Training Program at Penn”.
- Dowzicky PM, Shah AA, Barg FK, Eriksen WT, McHugh MD, Kelz RR. An Assessment of Patient, Caregiver, and Clinician Perspectives on the Post-Discharge Phase of Care. Annals of surgery. 2019 Jul.
- Berger I, Xia L, Wirtalla C, Dowzicky P, Guzzo TJ, Kelz RR. 30-day readmission after radical cystectomy: Identifying targets for improvement using the phases of surgical care. Canadian Urological Association Journal. 2019 Jul;13(7):E190.
- Sharoky CE, Collier KT, Wirtalla CJ, Sinnamon AJ, Neuwirth MG, Kuo LE, Roses RE, Fraker DL, Karakousis GC, Kelz RR. Hospitalization in the year preceding major oncologic surgery increases risk for adverse postoperative events. Annals of surgical oncology. 2017 Nov 1;24(12):3477-85.
- Bailey EA, Hoffman RL, Wirtalla C, Karakousis G, Kelz RR. Development and validation of a prediction model for patients discharged to post–acute care after colorectal cancer surgery. Surgery. 2017 Apr 1;161(4):1049-57.
Robert Krouse, MD - My current research program focuses primarily on cancer survivorship, including palliative care. My years of clinical experience as a Surgical Oncologist are an added benefit as a clinical researcher. I have a long history with inter-disciplinary research, leading and participating in teams that include surgeons, nursing researchers, epidemiologists, anthropologists, health economists, psychologists, nutritionists, physiologists, basic scientists, and statisticians. I have mentored 4 medical students, 11 residents, and 11 pre- and post-doctoral researchers. For this application, I can provide training in broad areas in Surgical Oncology Research including comparative effectiveness, patient-centered outcomes, palliative care, quality of life, mixed methods, clinical trials and cooperative group research. As Advisor to the SWOG Cancer Survivorship Committee, and Co-Chair of the developing SWOG Palliative and End-of-Life Care Committee, I help initiate, shepherd, and complete national trials related to cancer survivorship and palliative care issues. There are multiple studies at different levels of development that I have played a significant role with and will continue in the future. Presently I am Principal Investigator and national lead on an AHRQ-funded grant (AHRQ HS021491, Prospective Comparative Effectiveness Trial for Malignant Bowel Obstruction) which is in collaboration with SWOG cooperative group (S1316). This study has a novel hybrid design to examine the optimal treatment approach for patients with malignant bowel obstruction. Related to cancer survivorship, our team has had a focus primarily on rectal cancer survivorship and has established a greater understanding of long-term health-related quality of life (HRQOL) issues. We are currently designing interventions to improve the HRQOL for these survivors and their families. One current project I lead is a PCORI-funded grant (PCORI 1507-31690, Ostomy Telehealth for Cancer Survivors), which uses telehealth to provide an ostomy self-management curriculum to cancer survivors with ostomies. It is designed with patient-centered outcomes and is based on cancer survivor input from both a pilot study and from previous HRQOL studies on patient-identified challenges related to living with an ostomy. A related study I lead is an NIH-funded grant (R01 CA204193, Ostomy Telehealth Selfmanagement Training for Cancer Survivors) delivering the curriculum to rural populations. We are in the initial stages of planning an implementation study utilizing the NCORP system as an accrual base in conjunction with SWOG and other NCTN sites.
- Grant M, Ferrell B, Dean G, Uman G, Chu D, Krouse R. Revision and psychometric testing of the City of Hope Quality of Life-Ostomy Questionnaire. Qual Life Res. 2004 Oct;13(8):1445-57. PubMed PMID: 15503840.
- Krouse RS, Herrinton LJ, Grant M, Wendel CS, Green SB, Mohler MJ, Baldwin CM, McMullen CK, Rawl SM, Matayoshi E, Coons SJ, Hornbrook MC. Health-related quality of life among long-term rectal cancer survivors with an ostomy: manifestations by sex. J Clin Oncol. 2009 Oct 1;27(28):4664-70. PubMed PMID: 19720920; PubMed Central PMCID: PMC2754912.
- Grant M, McCorkle R, Hornbrook MC, Wendel CS, Krouse R. Development of a chronic care ostomy selfmanagement program. J Cancer Educ. 2013 Mar;28(1):70-8. PubMed PMID: 23104143; PubMed Central PMCID: PMC3578127.
- Wendel CS, Grant M, Herrinton L, Temple LK, Hornbrook MC, McMullen CK, Bulkley JE, Altschuler A, Krouse RS. Reliability and validity of a survey to measure bowel function and quality of life in long-term rectal cancer survivors. Qual Life Res. 2014 Dec;23(10):2831-40. PubMed PMID: 24890826; PubMed Central PMCID: PMC4236297.
Jason Moore, PhD - I have a strong track record developing, evaluating and applying statistical, machine learning and artificial intelligence algorithms and software for identifying genetic, genomic and proteomic biomarkers of clinical traits such as autoimmune disease. A central focus has been on developing translational bioinformatics methods such as multifactor dimensionality reduction (MDR) that embrace, rather than ignore, the complexity of human pathobiology. In addition to an NIH-funded translational bioinformatics research program, I serve as Director of the Institute for Biomedical Informatics and Senior Associate Dean for Informatics at the Perelman School of Medicine of the University of Pennsylvania. I also serve as Editor-in-Chief of the journal BioData Mining. I have trained more than 50 undergraduate, 20 graduate, and 15 postdoctoral students. I have previously served as the director of an interdisciplinary graduate training program at Dartmouth where I also led an NIH K25 training grant as PI. I am currently PI of an NHGRI T32 training grant. I will use these leadership and education experiences to assist with this training program.
- Ritchie MD, Hahn LW, Roodi N, Bailey LR, Dupont WD, Parl FF, Moore JH (2001). Multifactordimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet. 69(1):138-47. PMC1226028.
- Hu T, Sinnott-Armstrong NA, Kiralis JW, Andrew AS, Karagas MR, Moore JH (2011). Characterizing genetic interactions in human disease association studies using statistical epistasis networks. BMC Bioinformatics 12:364, PMC3215301.
- Askland K, Read C, Moore JH (2009). Pathways-based analyses of whole-genome association study data in bipolar disorder reveal genes mediating ion channel activity and synaptic neurotransmission. Hum Genet. 125(1):63-79. PMID: 19052778.
- Darabos C, White MJ, Graham BE, Leung DN, Williams SM, Moore JH. (2014a). The multiscale backbone of the human phenotype network based on biological pathways. BioData Min. 7(1):1. PMC3924922.
Katherine Nathanson, MD - I am an internationally recognized physician-scientist cancer geneticist/genomicist. Clinically, I manage patients with inherited cancer susceptibility syndromes, mainly those associated with brain, skin renal and neuroendocrine tumors. My research focuses on the elucidation of the inherited and somatic genetics of cancer, specifically in pheochromocytomas/paragangliomas (PCC/PGL), testicular germ cell tumors (TGCT), melanoma, and hereditary breast and ovarian cancers; I have over 300 publications in all these areas, with an H-score of 66. I am highly dedicated to training and education at all levels. I am the program director for the combined Internal Medicine/Clinical Genetics program at Penn Medicine, and MPI of a T32 post-doctoratraining grant in Genomic Medicine from NHGRI. I serve on the Residency Committee for Medical Genetics, on the admissions committee for the MD-PhD program and as co-PI for the Medical Genetics Research Training Grant. I also am a member of the Cancer Biology section of the Cell and Molecular Biology, and Genomics and Computational Biology graduate groups, serving on the latter’s admissions committee. I am highly committed to training and have trained 12 post-doctoral fellows, who have been very successful in obtaining funding and faculty positions. Within the past five years, five of my trainees have moved onto academic positions – Assistant Professors at the University of Pennsylvania, New York University and the University of Colorado, Denver, MD Anderson Cancer Center, and Director of Gynecologic Oncology Research at Christiana Care Health System, Delaware. With respect to this application, I can provide training in the area of inherited and somatic cancer genetics and genomics as associated with Surgical Oncology Research.
- Maxwell KN, Hart SN, Vijai J, Schrader KA, Slavin TP, Thomas T, Wubberhorst B, Ravichandran V, Moore RM, Hu C, Guidugli L, Wenz B, Domchek SM, Robson ME, Szabo C, Neuhausen SL, Weitzel JN, Offit K, Couch FJ, Nathanson KL. Evaluation of ACMG-guideline-based variant classification of cancer susceptibility and non-cancer-associated genes in families affected by breast cancer. Am J Hum Genet, 2016 May 5;98(5):801-17. PMID:27153395 PMCID:PMC4863474.
- Kanetsky PA, Mitra N, Vardhanabhuti S, Li M, Vaughn DJ, Letrero R, Ciosek SL, Doody DR, Smith LM, Weaver J, Albano A, Chen C, Starr JR, Rader DJ, Godwin AK, Reilly MP, Hakonarson H, Schwartz SM, Nathanson KL. Common variation in KITLG and at 5q31.3 proximate to SPRY4 predispose to testicular germ cell cancer. Nat Genet 2009; 41(7):811-5. PMCID:PMC2865677
- Bollag G, Hirth P, Tsai J, Zhang J, Ibrahim PN, Cho H, Spevak W, Zhang C, Zhang Y, Habets G, (25 authors) Chapman PB, Flaherty KT, Xu X, Nathanson KL, Nolop K: Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature 2010 Sep 30;467(7315):596-9. PMCID:PMC2948082
- Gordon JD, Lal P, Dondeti VR, Letrero R, Parekh KN, Oquendo CE, Greenberg RA, Flaherty KT, Rahmell K, Keith B, Simon MC, Nathanson KL. HIFα effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma. Cancer Cell 2008;14(6):435-46. PMCID:PMC2621440
Salary and Expenses
NIH postdoctoral stipend levels are set by the number of years of postgraduate training and are updated at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-20-070.html. Health insurance, travel, and some training expenses are included. Department of Surgery funds are used for additional salary support. Trainees may be eligible for financial support for formal coursework at Penn.
How to Apply
Please send the following 3 items.
1. Cover Letter
The letter should include:
- Career objectives
- Prior research experience
- Area of interest within cancer research
- Training goals for the T32 fellowship including whether you have interest in obtaining an advanced degree
- Proposed mentor (if decided) from the list of existing mentors above. You may propose a mentor at Penn not currently involved in the T32 program.
2. Updated CV
3. Letters of recommendation
Solicit a letter of recommendation from the Department Chair and the Residency Program Director regarding your career potential and the ability to commit to 2 years of research at Penn. It is acceptable to submit separate letters or a single letter signed by both.
Applications should be submitted as a SINGLE PDF file to:
Aly Trainor (Allyn.Trainor@pennmedicine.upenn.edu)
For More Information
Please contact Ronald P. DeMatteo MD, Chair of Surgery, at Ronald.Dematteo@pennmedicine.upenn.edu