Our training grant faculty is composed of 14 primary training grant mentors who are well respected researchers with outstanding records of education and training as well as five co-mentors who are young assistant professors with exciting research programs and who add significantly to our teaching curriculum and will train students and postdoctoral fellows in concert with more senior training grant faculty.
Ann Killary, Ph.D., is the program director of the T32 training program along with Dr. Wistuba who is the co-program director for the program. Her laboratory is interested in functional genomic approaches to elucidate the genetic mechanisms underlying the initiation and progression of breast cancer. Her lab is currently focusing on the characterization of a novel tumor suppressor and polarity regulator DEAR1 discovered in her laboratory and its role in the development and progression of breast and pancreatic cancers as well as its mutation/loss of function as a biomarker of poor prognosis in breast cancer.
In addition, her laboratory is investigating the earliest pathways
aberrant in pancreatic cancer for biomarker discovery. As a PI of a
biomarker discovery laboratory through the NCI’s Early Detection
Research Network, her laboratory developed a functional genomic
pathways based approach for biomarker discovery that has led to
biomarker panels that detect early stage pancreatic cancer in the
initiation and development, recruited immune cells establish a dynamic and close interaction with the neoplastic epithelium as well as with the fibrotic stroma, ultimately affecting tumor behavior. Her lab has taken several approaches: 1) Use of genetically-engineered mouse (GEM) models that mimic the development of human pancreatic cancer to dissect the role of immune cells in the regulation of cancer development; 2) Generation of GEM-immune reporter mice with the goal of performing multi-parametric cell sorting on particular types of immune cells at early and late stage of tumorigenesis for transcriptome analysis and for imaging studies aimed to determine cellular location and dynamics; 3) Utilization of bone marrow transplantation to test the functionality of specific immune cells or molecules in GEM models of pancreatic cancer; and, 4) Molecular characterization of the immune and epithelial human cells obtained from patients with pre-neoplastic lesions and pancreatic cancer to confirm the human significance of the experimental findings.
Dr. Krahe is using integrated approaches combining genomic and epigenomic profiling to dissect the complex genetic and epigenetic events underlying LFS tumorigenesis. To dissect the pathophysiological consequences of variant genes, his laboratory is generating suitable LFS mouse models. LFS predisposition and/or modifier genes may also be functionally important in other tumor types lacking a clear genetic predisposition. The molecular characterization and classification of sporadic cancers (head and neck and lung cancer, and gliomas) through genomics methodologies to identify genomic, epigenomic and transcriptomic changes underlying tumor initiation, progression and metastasis is another focus.
Scott Kopetz, M.D., Ph.D. is currently Deputy Chair of the Department of Gastrointestinal Medical Oncology and Program Leader of the GI Program of the Cancer Center Support Grant at UTMDACC. Dr. Kopetz is well versed in multidisciplinary care of and translational research for GI cancer patients. His laboratory is funded by multiple NIH-funded grants. He serves as chair of the Colon Cancer Task Force, and is Vice-Chair for Colon Cancer in the NSABP/RTG/GOG (NRG) Cooperative Group. Dr. Kopetz is a leader of the GI Cancer Center Support Grant at MD Anderson and the Colorectal Cancer Moonshot, a multi- disciplinary effort to improve the survival of this disease beyond incremental advances. He has authored over 300 peer-reviewed articles in respected scientific journals Scott Kopetz, M.D., Ph.D., such as New England Journal of Medicine, Nature Medicine, Journal of Clinical Oncology, Lancet, Nature Reviews Cancer, Cancer Research, Lancet Oncology, Clinical Cancer Research, and JAMA. He is a senior editor for Clinical Cancer Research. Dr. Kopetz has developed a translational and clinical trial program in BRAF-mutated colorectal cancer, which has resulted in addition of combination therapy with a BRAF inhibitor to the current treatment guidelines. He also co-lead the clinical trial resulting in the FDA-approval of nivolumab and ipilimumab for mismatch repair deficient tumors. He also is an innovator in the development and implementation of circulating tumor DNA into clinical management, including interrogation of mechanisms of resistance, evaluation of minimal residual disease, and integration into clinical trial designs. Further research efforts include the development of the Consensus Molecular Subtypes, an RNA- based methodology for CRC classification that is now being widely integrated in retrospective and clinical trial efforts.
Jason T. Huse, M.D., Ph.D., associate professor in the TMP department, will serve as a co-mentor for the T32 training grant. Dr. Huse and his research group are focused on characterizing the molecular mechanisms underlying primary and secondary brain cancer, with a specific focus on epigenetic and transcriptional mechanisms. Recent functional work from the Huse lab has delineated the epigenetic consequences of ATRX deficiency in malignant glioma, along with its impact on global genomic instability and the immune microenvironment. Multiple strategies for therapeutic targeting have emerged from this work, and additional pre-clinical studies are ongoing. Additionally, the lab is exploring early-stage etiological events in malignant glioma through extensive tissue profiling, correlating germline genetic polymorphisms with patterns of somatic alterations. Findings from these studies should inform downstream functional analyses directly implicating 3D-chromatin architecture in specific oncogenic events. Finally, the lab has performed extensive integrated molecular profiling of brain metastasis samples, identifying metabolic and immune-related phenotypes amenable to treatment strategies. Single-cell sequencing approaches are now being utilized to interrogate molecular heterogeneity within brain metastases and characterize its functional impact.
Timothy McDonnell, M.D., Ph.D., is a professor and will serve as mentor in the T32. His research program is devoted to mechanistic studies focused on clinically relevant issues including molecular mechanisms of therapeutic resistance. A variety of approaches are employed varying from histopathology to molecular biology. Until joining the Department of Hematopathology several years ago as Deputy Chair much of his research effort was devoted to studies of solid tumors, including cancers of the prostate and skin. Since joining MDACC his research focus has been reoriented to the study of hematolymphoid malignancies and the role of signaling events commonly altered in lymphoid malignancies such as those mediated by the sonic hedgehog and TP53 signaling axes. Further, his laboratory has devoted considerable effort to developing and adapting methodologies to undertake genome-wide assessments from human tumor samples, including archived formalin-fixed paraffin-embedded tissue. The ultimate goal of these studies is to enable rational stratification of patients with cancer and develop effective, mechanism-based therapies.