Charles H Williams III, PhD
Assistant Professor
Biomedical Research Focus
Dr. Charles Williams is a distinguished scientist with research interests centered on innovative approaches to drug discovery and deepening our understanding of molecular pathways in development and disease. His work is characterized by a commitment to translating basic science findings into novel therapeutic strategies. A cornerstone of Dr. Williams' research is the use of zebrafish as an in vivo model for phenotypic screening, allowing for the observation of compound effects on biological pathways in real-time. His expertise encompasses:
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Small Molecule Discovery: Identifying and developing small molecules to modulate critical biological processes.
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GPCRs and Signaling: Targeting G protein-coupled receptors (GPCRs), with a focus on GPR68, to develop inhibitors and elucidate signaling pathways relevant to disease.
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pH Regulation: Exploring the role of extracellular pH in both normal development and disease, including the creation of tools to dynamically measure extracellular pH.
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Cardiovascular Biology: Investigating heart failure, vascular development, and cardiomyocyte differentiation to identify modulators of cardiac function.
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In vivo Chemical Genetic Screens: Pioneering the development and application of in vivo chemical genetic screens, particularly in zebrafish, to identify novel modulators of biological processes.
Dr. Williams's work has contributed to the understanding of Hedgehog signaling, Wnt signaling, and the role of the tumor microenvironment in cancer. His research aims to bridge the gap between genetics, chemical biology, and therapeutic intervention, offering new hope for treating a range of conditions, from developmental disorders to cancer and cardiovascular diseases.
Notable Publications
Authors:
Leif R Neitzel, Maya Silver, Aaron H Wasserman, Samantha Rea, Charles C Hong, Charles H Williams
Publication date: 2025/1/22
Journal: Developmental Dynamics
Short Description:
This study introduces a novel transgenic zebrafish line expressing a pH-sensitive fluorescent protein, allowing researchers to visualize and measure extracellular pH changes in real-time. Using this model, they observed dynamic acidification patterns in developing tissues like the notochord, otic placode, and myotome, revealing new insights into the role of pH in development. The findings suggest that proper extracellular pH regulation is essential for normal physiological development and that this zebrafish line can be a valuable tool for studying acid homeostasis and disease states.
Authors:
Charles H Williams, Leif R Neitzel, Jessica Cornell, Samantha Rea, Ian Mills, Maya S Silver, Jovanni D Ahmad, Konstantin G Birukov, Anna Birukova, Henry Brem, Betty Tyler, Eli E Bar, Charles C Hong
Publication date: 2024/1/31
Journal: Experimental Hematology & Oncology
Short Description:
This study identifies Ogremorphin (OGM), a novel inhibitor of GPR68, a receptor activated by the acidic environment in glioblastoma. Blocking GPR68 signaling with OGM induces ferroptosis, a form of cell death, in glioblastoma cells, offering a potential therapeutic strategy. This research highlights GPR68 as a critical sensor for pro-tumorigenic signaling in glioblastoma, suggesting GPR68 inhibitors could be a promising treatment, especially alongside existing therapies.
Proton Sensing GPCR’s: The missing link to Warburg’s Oncogenic Legacy?
Authors:
Jessica Cornell, Samantha Rea, Leif R Neitzel, Charles H Williams and Charles C Hong
Publication date: 2024
Journal: Journal of cancer biology
Short Description:
This research explores how proton-sensing GPCRs may be the missing link between the Warburg effect and cancer. It proposes that these receptors, which respond to the acidic environment created by cancer's altered metabolism, transduce this signal into pro-oncogenic signals, potentially explaining why cancer cells favor inefficient energy production. Targeting these proton sensors could disrupt the synergy between the Warburg effect and oncogenic signaling, representing novel therapeutic opportunities.
Impaired reorganization of centrosome structure underlies human infantile dilated cardiomyopathy
Authors:
Young Wook Chun, Matthew Miyamoto, Charles H Williams, Leif R Neitzel, Maya Silver-Isenstadt, Adrian G Cadar, Daniela T Fuller, Daniel C Fong, Hanhan Liu, Robert Lease, Sungseek Kim, Mikako Katagiri, Matthew D Durbin, Kuo-Chen Wang, Tromondae K Feaster, Calvin C Sheng, M Diana Neely, Urmila Sreenivasan, Marcia Cortes-Gutierrez, Aloke V Finn, Rachel Schot, Grazia MS Mancini, Seth A Ament, Kevin C Ess, Aaron B Bowman, Zhe Han, David P Bichell, Yan Ru Su, Charles C Hong
Publication date: 2023
Journal: Circulation
Short Description:
This research article investigates the genetic basis of infantile dilated cardiomyopathy (iDCM), a severe heart condition in infants. The study identifies mutations in the RTTN gene, which encodes a centrosomal protein, as a novel cause of iDCM. Using patient-derived stem cells, CRISPR/Cas9 gene editing, and in vivo models like zebrafish and Drosophila, the researchers demonstrate that RTTN mutations impair centrosome reorganization, disrupt microtubule networks, and affect cardiomyocyte maturation and function. Ultimately, the study connects centrosome dysfunction to cardiac disease, highlights RTTN's importance in heart development, and suggests a potential therapeutic approach using a small molecule to restore centrosome organization and improve heart function in iDCM. These findings indicate the significance of developmentally programmed centrosome reorganization for proper cardiomyocyte structure and function, further expanding our understanding of the genetic origins of heart disease.