Detailed understanding of molecular function in biological systems requires information about the 3D structures of macromolecules. The wealth of information available from such studies provides novel and powerful insights into function. Chemical biology, the modulation of protein function by small molecules, provides tool compounds to explore biological function as well as novel therapeutics for the clinic. The tools of imaging, detection, and drug delivery emerge from chemical biology efforts. The merging of the structural biology and chemical biology faculty brings together two groups that speak the same language, the language of molecular structure, making this a natural grouping. The overarching goal of the Chemical & Structural Biology (CSB) Program is to facilitate this dialogue in ways that accelerate understanding, detection, and treatment of cancer. The Program leader is John H. Bushweller, PhD, Professor of Molecular Physiology and Biological Physics, and the co-leader is Kevin R. Lynch, PhD, Professor of Pharmacology and Biochemistry & Molecular Genetics. The Program currently consists of 23 members and 6 associate members from seven different departments spanning three different schools at UVA. This includes the Chemistry Department, providing unique cross- campus opportunities to bring the power of chemistry to bear on cancer. Six of these individuals were recruited to UVA since the last renewal. Total extramural funding for the Program exceeds $12M, including over $2.4M from the NCI and over $8.7M from other NIH institutes. The group members rely heavily on Cancer Center supported infrastructure, particularly the Biomolecular Analysis Core and NMR instrumentation. Pilot grant support of CSB members has shown a clear return on investment with several NCI funded grants emerging from work supported originally with pilot grant support. The many activities and interactions have led to 276 publications, of which 18% were inter-programmatic publications and 18% were intra-programmatic publications since the last renewal.

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National Cancer Institute (NCI)
Center Core Grants (P30)
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Subcommittee H - Clinical Groups (NCI)
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University of Virginia
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Olmez, Inan; Zhang, Ying; Manigat, Laryssa et al. (2018) Combined c-Met/Trk Inhibition Overcomes Resistance to CDK4/6 Inhibitors in Glioblastoma. Cancer Res 78:4360-4369
Parini, Paolo; Melhuish, Tiffany A; Wotton, David et al. (2018) Overexpression of transforming growth factor ? induced factor homeobox 1 represses NPC1L1 and lowers markers of intestinal cholesterol absorption. Atherosclerosis 275:246-255
Banizs, Anna B; Huang, Tao; Nakamoto, Robert K et al. (2018) Endocytosis Pathways of Endothelial Cell Derived Exosomes. Mol Pharm :
Jia, Deshui; Augert, Arnaud; Kim, Dong-Wook et al. (2018) Crebbp Loss Drives Small Cell Lung Cancer and Increases Sensitivity to HDAC Inhibition. Cancer Discov 8:1422-1437
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

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