Molecular origins and evolution to treatment resistance in genitourinary cancers - PROJECT SUMMARY
Under Unit Director Dr. Eliezer Van Allen's leadership, the Van Allen laboratory's NCI funded research programs
study genitourinary (GU) cancers (prostate, bladder, kidney, testes), with a focus on understanding treatment
resistance in these diseases through integrative computational and molecular approaches grounded in the
patient experience. With her multidisciplinary training and collaborative leadership, Research Specialist Dr. Jihye
Park has been an integral part of these research programs contributing to various discovery and novel
computational methods. Our research programs led to the discovery of the molecular basis of selective
chemosensitivity in bladder and testes cancers, and biological understanding of androgen inhibitor resistance in
prostate cancer, creating new drug discovery paradigms and means of patient stratification. We also developed
integrative computational and experimental approaches to discover the interaction relevant to treatment
resistance across the tumor, germline, and immune axes with our patient-centered paradigm in GU cancers.
Furthermore, we discovered tumor-intrinsic factors determining cancer immunotherapy in solid tumors, directly
invoking chromatin dysregulation as a cause of selective immunotherapy response and forming the basis for
new files of drug development and therapeutic combinations. Despite these advances, the majority of patients
with advanced GU cancers still experience resistance to therapies and the biological relevance and interplay of
specific germline, somatic, or immune systems in these cancers are still largely unknown. Furthermore, we face
computational challenges to handle vast amounts of new types of data to analyze efficiently. Dr. Park is now
leading the effort to utilize integrated patient-centered approaches, specifically longitudinal single cell
transcriptional and whole genome and epigenetic characterization of tumors, to understand the biological basis
of molecular sensitization with tumor evolution perspectives and determine the paradigms that drive lethal
immunotherapy resistant disease in GU cancers. Dr. Park will also contribute to the development of
comprehensive and scalable analytic tools that can integrate multi-omics data and study systems level
interactions between germline, somatic, and immune systems. These methods will be implemented within an
open cloud-based platform (Terra) and amplify collaborations within the cancer community. Overall, Dr. Park's
recent and ongoing contributions aim to reveal the integrated molecular factors that drive lethal disease in GU
cancers and elucidate the biology of these processes, toward translation of effective therapeutic and patient
stratification modalities, and broader accessibility of comprehensive computational methods utilizing cutting edge
molecular profiling approaches. With Unit Director Dr. Eliezer Van Allen, Dr. Park's leadership and scientific and
computational efforts will continue to establish an interdisciplinary and highly collaborative group with scientists
from diverse scientific domains driving these comprehensive clinical computational research programs.
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