David Weber

Associate 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
2022
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.
The calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling.
An Extract of Taro (Colocasia esculenta) Mediates Potent Inhibitory Actions on Metastatic and Cancer Stem Cells by Tumor Cell-Autonomous and Immune-Dependent Mechanisms.
Drug Delivery Systems: A Few Examples of Applications, Drug Cargoes, and Administration Routes.
1HN, 13C, and 15N backbone resonance assignments of the SET/TAF-1β/I2PP2A oncoprotein (residues 23-225).
A method to improve quantitative radiotracing-based analysis of the in vivo biodistribution of drug carriers.
The Importance of Therapeutically Targeting the Binary Toxin from Clostridioides difficile.
Engineering subtilisin proteases that specifically degrade active RAS.
Intracellular Delivery of Active Proteins by Polyphosphazene Polymers.
Specificity of Molecular Fragments Binding to S100B versus S100A1 as Identified by NMR and Site Identification by Ligand Competitive Saturation (SILCS).
Small molecules inhibitors of the heterogeneous ribonuclear protein A18 (hnRNP A18): a regulator of protein translation and an immune checkpoint.
2020
1HN, 13C, and 15N resonance assignments of the Clostridioides difficile receptor binding domain 2 (CDTb, residues 757-876).
Intertwined mechanisms define transport of anti-ICAM nanocarriers across the endothelium and brain delivery of a therapeutic enzyme.
Correction to: 1HN, 13C, and 15N resonance assignments of human calmodulin bound to a peptide derived from the STRA6 vitamin A transporter (CaMBP2).
Structure of the cell-binding component of the Clostridium difficile binary toxin reveals a di-heptamer macromolecular assembly.
2019
Galeterone and The Next Generation Galeterone Analogs, VNPP414 and VNPP433-3β Exert Potent Therapeutic Effects in Castration-/Drug-Resistant Prostate Cancer Preclinical Models In Vitro and In Vivo.
An asymmetry that leads to activity.