David Weber

Co-Director, IBBR

Weber Group

Contact

Email: DWeber@som.umaryland.edu

Call: (240) 314-6163

Education

  • Postdoctoral Fellowship, Johns Hopkins School of Medicine, 1988-1992
  • Ph.D., Chemistry, University of North Carolina-Chapel Hill, 1988
  • B.S., Chemistry, Muhlenberg College, 1984

Profile

As Director of the Center for Biomolecular Therapeutics (CBT) located within IBBR, Dr. Weber manages state-of-the-art scientific studies that investigate mechanisms involved in disease states and develops drugs to treat them. His laboratory is one of many in the CBT developing small-molecule inhibitors geared toward treating cancer, diabetes, and infectious disease.

Figure SEQ Figure \* ARABIC 1.  S100 proteins in cancer.  Elevated levels of several S100 proteins contribute to several cancer phenotypes in human cancers, including malignant melanoma.   Inhibitors developed in the Weber laboratory using structure-based drug design methods show promise and are under consideration for future therapeutic development in The Center for Biomolecular Therapeutics (CBT).

One such project involves studies of the structure, function, and inhibition of the S100 family of calcium-binding proteins. The Weber lab has shown that one particular S100 protein called S100B is not only an important marker for the prognosis of malignant melanoma patients, but that it also contributes to the disease state. Specifically, higher levels of S100B was shown to eliminate an important natural tumor suppressor called p53 (Figure 1). To address this problem, they developed small molecules inhibitors of S100B to restore active p53. Such molecules have the potential to help patients where other therapies are not effective, including cancer immunology approaches. To achieve this goal, structure-based drug-design technologies are used to develop experimental drugs that are more potent and safer than existing inhibitors and are being evaluated in malignant melanoma mouse models.

The CBT comprises seven research sections encompassing initial discovery through product development.

If successful, the next steps will be to develop such inhibitors safe for use in a human clinical trial with the long-range goal of helping provide new treatment options to malignant melanoma patients. Malignant melanoma is the fifth and seventh most common cancer among men and women, respectively, with more than 60,000 cases per year.

CBT Overview

CBT comprises seven research sections, each leveraging the intellectual capital of The University System of Maryland (USM) and an entrepreneurial, scientific environment to excel in aspects of therapeutic development and treatment. This combination delivers a comprehensive approach to the science of advancing human health, from discovery to therapeutic development.

Targeting infectious disease, cancer, diabetes, and neurological diseases, CBT researchers and scientists develop potential treatments to fight disease and improve quality of life. From target identification through testing, CBT uses a suite of technological and biomedical tools not found collectively in any other institution in the United States. Capitalizing on the depth and breadth of expertise found at the University of Maryland School of Medicine, and with close collaboration across University Systems of Maryland, CBT performs a number of services integral to the fight against disease, including world-renowned research in medicinal chemistry, structural biology, protein engineering, and biophysics.

 

Publications
2024
Unveiling the intricate role of S100A1 in regulating RyR1 activity: A commentary on "Structural insights into the regulation of RyR1 by S100A1".
Structural and Functional Insights into the Delivery Systems of Bacillus and Clostridial Binary Toxins.
Deuterium spin relaxation of fractionally deuterated ribonuclease H using paired 475 and 950 MHz NMR spectrometers.
Deciphering S100B Allosteric Signaling: The Role of a Peptide Target, TRTK-12, as an Ensemble Modulator.
2023
Dendritic Cell-Mediated Cross-Priming by a Bispecific Neutralizing Antibody Boosts Cytotoxic T Cell Responses and Protects Mice against SARS-CoV-2.
Initial exploration of a novel fusion protein, IL-4/IL-34/IL-10, which promotes cardiac allograft survival mice through alloregulation.
VNLG-152R and its deuterated analogs potently inhibit/repress triple/quadruple negative breast cancer of diverse racial origins in vitro and in vivo by upregulating E3 Ligase Synoviolin 1 (SYVN1) and inducing proteasomal degradation of MNK1/2.
Salinization Dramatically Enhance the Anti-Prostate Cancer Efficacies of AR/AR-V7 and Mnk1/2 Molecular Glue Degraders, Galeterone and VNPP433-3β Which Outperform Docetaxel and Enzalutamide in CRPC CWR22Rv1 Xenograft Mouse Model.
Transglutaminase 2 binds to the CD44v6 cytoplasmic domain to stimulate CD44v6/ERK1/2 signaling and maintain an aggressive cancer phenotype.
Croquemort elicits activation of the immune deficiency pathway in ticks.
Integrated Covalent Drug Design Workflow Using Site Identification by Ligand Competitive Saturation.
Targeted Degradation of Androgen Receptor by VNPP433-3β in Castration-Resistant Prostate Cancer Cells Implicates Interaction with E3 Ligase MDM2 Resulting in Ubiquitin-Proteasomal Degradation.
Structure-Based Design of Potent Iminosugar Inhibitors of Endoplasmic Reticulum α-Glucosidase I with Anti-SARS-CoV-2 Activity.
2022
1H, 13C, and 15N assignments of the mRNA binding protein hnRNP A18.
Computer-Aided Drug Design: An Update.
Novel AR/AR-V7 and Mnk1/2 Degrader, VNPP433-3β: Molecular Mechanisms of Action and Efficacy in AR-Overexpressing Castration Resistant Prostate Cancer In Vitro and In Vivo Models.
Transcriptome profiling reveals that VNPP433-3β, the lead next-generation galeterone analog inhibits prostate cancer stem cells by downregulating epithelial-mesenchymal transition and stem cell markers.
2021
Nano-Assembly of Quisinostat and Biodegradable Macromolecular Carrier Results in Supramolecular Complexes with Slow-Release Capabilities.
Sulforaphane covalently interacts with the transglutaminase 2 cancer maintenance protein to alter its structure and suppress its activity.
Physiologically Relevant Free Ca2+ Ion Concentrations Regulate STRA6-Calmodulin Complex Formation via the BP2 Region of STRA6.