Detailed understanding of molecular function in biological systems requires information about the three dimensional structures of macromolecules. The wealth of information available from studies in structural biology provides novel and powerful insights into function. Chemical biology, the modulation of protein function by small molecules, provides both tool compounds to explore biological function as well as leads for development of therapeufic agents. The merging of the structural and chemical biology faculfies brings together two groups that speak the same language, the language of molecular structure, making the merger a natural grouping. The Chemical and Structural Biology Program (CSB) defines its overarching goal as the facilitation of this dialogue to accelerate understanding and treatment of cancer. CSB focuses this goal around four thematic elements;(1) Structural and chemical biology targeting transcription factors. (2) Structural and chemical biology targeting signaling molecules, (3) Advancing structural biology technologies, (4) Chemical biology for imaging, detection, and diagnosis. John H. Bushweller, PhD, Professor of Molecular Physiology and Biological Physics, leads the Program with Kevin R. Lynch, Professor of Pharmacology and of Biochemistry and Molecular Genetics. CSB currenfiy comprises 19 Members and 6 Associate Members from seven different departments at the University of Virginia (UVA). By including the Chemistry Department, the Program provides unique, cross-campus opportunities to bring the power of chemistry to bear on cancer. CSB leadership has recruited seven of these individuals to UVA since the last renewal. Total extramural funding for the Program exceeds $11 million, including more than $1.7 million from the National Cancer Insfitute (NCI) and more than $8.8 million from other National Insfitutes of Health (NIH) entities. The Program Members rely heavily on Cancer Center-supported infrastructure, particulariy the Biomolecular Analysis Facility and NMR instrumentation. Pilot Funds and research retreats have provided the framework for productive collaborations among UVA Cancer Center members. The many activifies and interactions of CSB Members have led to 287 publicafions, of which 29% were interprogrammatic publicafions and 15% were intra-programmatic publications since the last renewal.

Public Health Relevance

Understanding the structures of proteins, how they become altered in cancer, and how to design drugs that inhibit their altered behavior is key to improvements in cancer treatment and detection, and is the goal of the Chemical and Structural Biology Program.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Center Core Grants (P30)
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Subcommittee G - Education (NCI)
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Manukyan, Arkadi; Kowalczyk, Izabela; Melhuish, Tiffany A et al. (2018) Analysis of transcriptional activity by the Myt1 and Myt1l transcription factors. J Cell Biochem 119:4644-4655
Engelhard, Victor H; Rodriguez, Anthony B; Mauldin, Ileana S et al. (2018) Immune Cell Infiltration and Tertiary Lymphoid Structures as Determinants of Antitumor Immunity. J Immunol 200:432-442
Martins, André L; Walavalkar, Ninad M; Anderson, Warren D et al. (2018) Universal correction of enzymatic sequence bias reveals molecular signatures of protein/DNA interactions. Nucleic Acids Res 46:e9
Michaels, Alex D; Newhook, Timothy E; Adair, Sara J et al. (2018) CD47 Blockade as an Adjuvant Immunotherapy for Resectable Pancreatic Cancer. Clin Cancer Res 24:1415-1425
Shi, Lei; Li, Kang; Guo, Yizhan et al. (2018) Modulation of NKG2D, NKp46, and Ly49C/I facilitates natural killer cell-mediated control of lung cancer. Proc Natl Acad Sci U S A 115:11808-11813
Yang, Jun; LeBlanc, Francis R; Dighe, Shubha A et al. (2018) TRAIL mediates and sustains constitutive NF-?B activation in LGL leukemia. Blood 131:2803-2815
Kulling, Paige M; Olson, Kristine C; Hamele, Cait E et al. (2018) Dysregulation of the IFN-?-STAT1 signaling pathway in a cell line model of large granular lymphocyte leukemia. PLoS One 13:e0193429
Grant, Margaret J; Loftus, Matthew S; Stoja, Aiola P et al. (2018) Superresolution microscopy reveals structural mechanisms driving the nanoarchitecture of a viral chromatin tether. Proc Natl Acad Sci U S A 115:4992-4997
Knapp, Kiley A; Pires, Eusebio S; Adair, Sara J et al. (2018) Evaluation of SAS1B as a target for antibody-drug conjugate therapy in the treatment of pancreatic cancer. Oncotarget 9:8972-8984
Kedzierska, Katarzyna Z; Gerber, Livia; Cagnazzi, Daniele et al. (2018) SONiCS: PCR stutter noise correction in genome-scale microsatellites. Bioinformatics 34:4115-4117

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