Education
| BS | Chemistry/Premedicine | Polytechnic Institute of Brooklyn | Brooklyn, N.Y. |
| PhD | Chemistry | University of Nebraska | Lincoln, Neb. |
Research Area
Nucleotide receptors and signaling in inflammation, cardiovascular and autoimmune exocrine disease.
Research Description
Nucleotide receptors (P2 receptors) are present in nearly all cells and tissues where they mediate diverse functions including the regulation of platelet aggregation, muscle contraction, neurotransmission, insulin secretion, epithelial ion transport, wound healing and cell growth. We have isolated the first human P2 receptor gene and expressed it in mammalian cell lines that normally lack this receptor. These expression systems have enabled us to identify and purify the P2 receptor protein and current research is directed towards investigating structural features of the receptor that affect its functions. We have cloned or obtained 11 different P2 receptor subtypes belonging to 2 different receptor superfamilies and we are investigating the mechanisms of receptor activation, desensitization, and signal transduction in a variety of tissues in relation to normal physiological functions and disease.
We have undertaken efforts to determine the molecular mechanisms whereby activation of P2 receptors can be employed for the treatment of human disease. Studies are directed towards: 1) determining the intracellular pathways that enable P2 receptors to promote chloride secretion in cystic fibrosis (CF) epithelium to effectively bypass the genetic defect in chloride transport that underlies CF; 2) investigating the integrin-like properties of P2 receptors in the cardiovascular system in relation to the effects of extracellular nucleotides on platelet aggregation, vasorelaxation and contraction, atherogenesis and inflammatory responses mediated by monocyte adherence to endothelium, responses that are associated with the early stages of atherosclerosis and diabetes; 3) understanding the role of P2 receptors in neuronal apoptosis and reactive astrogliosis associated with Alzheimer’s and other neurodegenerative diseases; 4) determining the role of nucleotide receptors in salivary gland inflammation and regeneration to design better treatments for Sjögren’s syndrome; and 5) identifying the molecular mechanisms whereby dietary nutriceuticals prevent disease. Our laboratory possesses the relevant molecular reagents and cell systems needed to progress these projects and participating graduate students gain experience in a variety of techniques in molecular and cell biology.
Notable Honors and Service
- International Association for Dental Research Distinguished Scientist Award for Salivary Research, 2016
- Outstanding Scientists Award-Fellows Award, The Academy of Science-St. Louis, 2020
- Fellow of The Academy of Science-St. Louis, elected in 2020
- College of Agriculture, Food and Natural Resources “Drivers of Distinction” Award, 2020
- NIH/NIDCR Board of Scientific Counselors, Division of Intramural Research, Regular Member, February 2019-February 2024
- Siteman Cancer Center, Washington University, Associate Member, appointed in August 2021
Selected Publications
Woods, L.T., Jasmer, K.J., Muñoz Forti, K., Shanbhag, V.C., Camden, J.M., Erb, L., Petris, M.J., and Weisman, G.A. (2020) P2Y2 Receptors Mediate Nucleotide-induced EGFR Phosphorylation and Stimulate Proliferation and Tumorigenesis of Head and Neck Squamous Cell Carcinoma Cell Lines. Oral Oncol. 109, 104808.
Gudekar, N.S., Shanbhag, V.C., Wang, Y., Ralle, M., Weisman, G.A., and Petris, M.J., (2020) Metallothioneins Regulate ATP7A Trafficking and Control Cell Viability During Copper Deficiency and Excess. Scientific Reports 10, 7086.
dos Santos, H.T., Kim, K. Okano, T., Camden, J., Weisman, G.A., Baker, O.J., and Nam, K. (2020) Cell Sheets Restore Secretory Function in Wounded Mouse Submandibular Glands. Cells 9(12), 2645.
Wang, J., Harvey, J., Garrad, R., Huxley, V.H., Erb, L., and Weisman, G.A. (2020) Simple, Reliable Isolation, Purification and Cultivation of Murine Skeletal Muscle Microvascular Endothelial Cells. J. Biomed. Sci. Eng., 13(12), 290-299.
Karagozoglu, K.H., Helder, M.N., Bot, J., Kamp, O., Forouzanfar, T., Brand, H., Cha, S., Weisman, G.A., Bartelink, I.H., Vissink, A., and Jager, D.H.J. (2020) Intra-operative Visualization and Treatment of Salivary Glands in Sjögren’s Syndrome by Contrast-enhanced Ultrasound Sialendoscopy (CEUSS): Protocol for a Phase I Single-center, Single-arm, Exploratory Study. BMJ Open. 10.1136/bmjopen-2019-033542 http://bmjopen.bmj.com 30 September 2020. PMID: 32998913 PMCID: PMC7528357.
Jasmer, K.J., Woods, L.T., Muñoz Forti, K., Martin, A.L., Camden, J.M., Colonna, M., and Weisman, G.A. (2021) P2Y2 Receptor Antagonism Resolves Sialadenitis and Improves Salivary Flow in a Sjögren’s Syndrome Mouse Model. Arch. Oral Biol. (in press). NIHMS1671346.
Spratt, A., Kannan, S., Woods, L.T., Weisman, G.A., Quinn, T.P., Lorson, C.L., Sonnerborg, A., Byrareddy, S., and Singh, K. (2021) Factors associated with emerging and re-emerging SARS-CoV-2. Comput. Struct. Biotechnol. J. 19: 3799-3809. PMID: 33791700.
Gilman, K., Camden, J.M., Woods, L.T., Weisman, G.A., and Limesand, K.H. (2021) Indomethacin Treatment Post-Irradiation Improves Mouse Parotid Salivary Gland Function via Modulation of Prostaglandin E2 Signaling. Front. Bioeng. Biotechnol. (in press).
Current Funding
Targeting P2 receptors to restore salivary and lacrimal gland function in Sjogren’s syndrome
Investigators: Gary Weisman; Carisa Petris; Seunghee Cha
Funding Source: NIH-NIDCR R01
Amount Received: $3,401,180
Dates: 3/1/2021 – 2/28/2026
P2Y2 receptor-integrin interactions in Spike- and ACE2-mediated SARS-CoV-2 entry in lung alveolar epithelial cells
Investigators: Gary Weisman; Kamlendra Singh
Funding Source: American Lung Association
Amount Received: $200,000
Dates: 11/23/2020 – 11/22/2022
Novel role for the P2Y2 receptor in the autoimmune disease Sjogren’s syndrome
Investigators: Gary Weisman; Laurie Erb; Julian Ambrus
Funding Source: NIH-NIDCR-R01
Amount Received: $3,133,560
Dates: 09/22/2016 – 08/31/2022 (NCE)
Novel role for the P2Y2 receptor in the autoimmune disease Sjogren’s syndrome: Supplement on COVID-19 infection of oral epithelium
Investigators: Gary Weisman; Laurie Erb; Julian Ambrus
Funding Source: NIH-NIDCR-R01
Amount Received: $232,102
Dates: 09/1/2020 – 08/31/2022 (NCE)
The role of TGFbeta in development and function of salivary gland innate lymphoid cells
Investigators: Marco Colonna; Gary Weisman
Funding Source: NIH-NIDCR-R01
Amount Received: $3,775,304
Dates: 12/01/2016 – 11/30/2022 (NCE)
Copper and iron in nutritional immunity
Investigators: Michael Petris; Gary A. Weisman
Funding Source: NIH-R01
Amount Received: $2,544,332
Dates: 04/01/2018 – 03/21/2023
Molecular Mechanisms of Drug Resistance in Head and Neck Squamous Cell Carcinoma
Investigators: Mark Hannink; Gary A. Weisman
Funding Source: MU TRIUMPH Gran
Amount Received: $99,902
Dates: 05/31/2021 – 04/30/2023
Novel use of P2X7 receptor antagonists to protect salivary glands in PSMA-617 targeted radiotherapy for prostate cancer
Investigators: Tom Quinn; Gary Weisman
Funding Source: MU TRIUMPH Grant
Amount Received: $100,000
Dates: 05/31/2021 – 04/30/2023