David C. Williams, Jr.

David C. Williams, Jr. is a Professor in the Department of Pathology and Laboratory Medicine at the University of North Carolina at Chapel Hill School of Medicine, where he holds a dual MD/PhD appointment. He is a member of the UNC Lineberger Comprehensive Cancer Center, focusing his research on structural and biophysical mechanisms of epigenetic regulation. His laboratory investigates protein-protein and protein-DNA interactions central to macromolecular complexes involved in gene expression control, with particular emphasis on the NuRD complex and MBD2 protein.

Williams' research program centers on understanding how epigenetic signals, particularly DNA methylation, regulate gene expression through structural mechanisms. His laboratory employs nuclear magnetic resonance (NMR) spectroscopy, isothermal titration calorimetry, circular dichroism, and surface plasmon resonance to characterize the structure and dynamics of protein complexes. A major focus has been the methyl-cytosine binding domain protein 2 (MBD2) and its role in recruiting the NuRD complex to methylated DNA, leading to gene silencing. His work has revealed critical structural details of how MBD2 binds DNA, interacts with other NuRD components through coiled-coil domains, and how these interactions can be targeted therapeutically.

Analysis of Williams' recent publications reveals a consistent trajectory toward increasingly sophisticated structural characterization of epigenetic regulatory complexes. His work spans from fundamental biophysical characterization of protein-DNA interactions to translational applications in cancer therapy, particularly in understanding how epigenetic silencing contributes to tumor suppressor gene inactivation. The research demonstrates growing integration of single-molecule techniques, nanofluidic analysis, and cross-species evolutionary perspectives to understand conserved epigenetic mechanisms.

• PRAT Fellowship, National Institute of General Medical Sciences (2001-2004)
• Medical Scientist Training Program, University of Virginia (1990-1998)
• Keystone Award for Outstanding Scientific Contribution, Keystone Symposium (1996)
• Alpha Omega Alpha national medical honor society (1992)
• Graduated with Highest Honors, College of William and Mary (1990)

Williams leads an active research program investigating the structural basis of epigenetic regulation, with implications for developing inhibitors of methylation-dependent gene silencing. His laboratory has established critical structure-function relationships for MBD2-NuRD interactions, demonstrating that disrupting specific protein-protein interfaces can block tumor cell growth. The research has potential applications in reactivating silenced tumor suppressor genes in cancer therapy. Williams collaborates extensively with researchers across multiple institutions, evidenced by co-authorship on numerous interdisciplinary studies spanning structural biology, cancer research, and hematology.

The Williams Laboratory maintains a strong focus on the structural and dynamic properties of epigenetic regulatory complexes, particularly examining how MBD2 recognizes methylated DNA and recruits the NuRD complex. Current research directions include developing peptide inhibitors targeting critical protein-protein interfaces within the NuRD complex, studying the distribution of MBD proteins on methylated DNA, and investigating the role of intrinsically disordered regions in complex assembly. The lab's work bridges fundamental structural biology with potential therapeutic applications in cancer and other diseases involving epigenetic dysregulation.