About the Costa Lab

Blaise Costa is a Pharmacology Professor at Edward Via Virginia College of Osteopathic Medicine. His office and laboratory are located at Virginia Tech Center for One Health Research facility. Costa lab is interested in developing novel treatment strategies for neurological and psychiatric disorders that affect human beings and other animals. With this aim, they are studying a family of glutamate and glycine gated excitatory neurotransmitter receptor expressed throughout the mammalian central nervous system. This N-methyl-D-aspartate (NMDA) binding protein is known as NMDA receptor. Normal activation of NMDA receptor is essential for higher order brain functions including cognition, decision making, simulating future events by consolidating memories from present and past experiences. Dysfunction of NMDA receptor is implicated in several neurological and psychiatric disorders. Costa and colleagues work to identify drug-like compounds to modulate NMDA receptors. As a remarkable outcome of continued effort, they recently discovered a novel family of agonist concentration dependent NMDA receptor modulators. To translate these compounds into clinically useful drug candidates, Costa lab is currently studying them on in-vitro and in-vivo models of neurological and other disorders that affect human lives. 

Project 1

  • Support: 10382 Virginia Tech ICTAS & VCOM seed grant -Active

  • 16SDG27480023 (Costa) AHASDG: Development and pharmacological characterization of mechanistically distinct NMDA receptor allosteric modulators. -Completed.

Most pharmacological agents that are binding at NMDA receptor agonist binding domain (ABD) cleft are weakly selective for the GluN2 subunit of interest. Therefore we are currently targeting the less conservative GluN1/2 ABD interface to design subtype-selective positive and negative allosteric modulators. Two electrode voltage clamp and patch-clamp electrophysiology techniques are used to study the NMDA receptor function. Computational modeling, docking, and molecular dynamics simulation techniques are used to predict potential drug targets and ligand designing.

Project 2

  • Support: 1 R15 AT010789-01A1 (Costa) : To identify the role of brain lymphatic systems in cranial osteopathic manipulative therapy on animal models of Alzheimer’s disease. -Active

  • American Osteopathic Association grant (# 1915733): Clearance of Brain Metabolic Waste in a Natural Animal Model of Alzheimer’s Disease by Cranial Osteopathic Manipulation -Completed

Novel "Mechanoceutics TM" Treatment Strategy for Alzheimer’s Disease

Studying potential use of mild mechanical pressure for the treatment of Alzheimer’s disease. This idea was conceived based on the knowledge about the existence of brain lymphatic vessels and the capability of cranial osteopathic manipulation (COM) to improve fluid circulation in the brain. COM treated eighteen month old rats exhibit improvement in spatial learning and memory, reduction in Aβ plaques and changes in substrates associated with CNS fluid clearance. Currently, continuing this work using transgenic rat (TgF344-AD) model of Alzheimer’s disease.

There are numerous animal models available for Alzheimer’s disease. The most commonly used models are transgenic animals that overexpress amyloid precursor protein (APP), a precursor for A-beta that accumulates in the brain and initiates the Alzheimer’s disease pathology . At toxic levels, such amyloid accumulation causes characteristics of Alzheimer’s disease, evidenced by defects in learning and memory. We use a transgenic rat (TgF344-AD) model for Alzheimer’s disease that mimics age-dependent cognitive decline and is more translatable to humans compared to other models. These animals express human amyloid precursor-protein (APP) gene with two Swedish mutations (K595N & M596L) and exon-9 deleted presenilin-1 gene. Following are the techniques used for this study:

  • Spatial learning and memory assay using the Morris water maze.

  • Positron emission tomography (PET) imaging for A-beta plaque using FDA-approved radiotracer, Florbetapir F18 injection (Amyvid).

  • Biochemical analysis of brain tissue samples

 

Current Lab Members

Blaise Costa, MPharm, PhD 

Principal Investigator
PhD in Psychopharmacology
National Institute of Mental Health and Neurosciences (NIMHANS)
Bangalore, India

Headshot of Seth Boehringer.

Seth Boehringer

Research Assistant
HNFE-2023
Virginia Tech

TEVC electrophysiology assays on novel NMDA receptor modulators.

Immunoassays to identify NMDA receptor activation induced changes in intracellular signaling mechanisms

Headshot of De'Yana Hines.

De'Yana N. Hines, B.S.

Ph.D. Student
School of Biomedical Engineering & Sciences
Virginia Tech
B.S. in Biological Engineering
University of Georgia

Studying mechanisms of a non-Pharmacological approach to improve brain fluid circulation using naturally aged and transgenic (TgF344-AD) rat model of Alzheimer’s disease

Headshot of Nakia Phillip.

Nakia Phillip, B.S.

Research Assistant
B.S. in Neuroscience
Virginia Tech

Studying the effect of glutamate concentration dependent NMDAR modulators on disease causing GRIN mutations and expression of post-synaptic signaling molecules.

VCOM students on research rotation

Photo coming soon.

Caleb Brown, B.A. 

Medical Student at VCOM
B.A. in Biology & Philosophy
University of Virginia

Incorporating human GRIN 2A mutants in rat recombinant GluN2A subunits and pharmacological characterization.

Photo coming soon.

Leah Dunn, B.S. 

Medical Student at VCOM
B.S. in Biomedical Science
Florida Institute of Technology

Studying the effect of glutamate concentration dependent NMDAR modulators on the expression of post-synaptic signaling molecules.

Photo coming soon.

Joseph Piwowarski, B.S. 

Medical Student at VCOM
B.S. in Interdisciplinary Studies
Liberty University

Proteomic analysis of cranial osteopathic manipulation induced changes in TgF344-AD rat brain hippocampus.

Photo coming soon.

Anshul Ramanathan, B.S. 

Medical Student at VCOM
B.S. Biological Sciences
Drexel University

Transcriptome analysis of cranial osteopathic manipulation induced changes in TgF344-AD rat brain hippocampus.

 

Alumni

  • Alyssa Ingram: 5/2021 -7/2022
  • Rehan Razzaq: 07/2019 - 9/2021
  • Lina Kwapisz: 07/2019 – 6/2021
  • Patrick Rafael: 09/2020 -7/2021
  • Brittney Mehrkens: 07/2019 – 1/2021
  • Tullia Johnston: 08/2018 – 6/2019
  • Bryanna Vacca: 06/2018 – 6/2019
  • Anushri Wagner: 01/2018 – 12/2019
  • Mike Mykins: 06/2017 - 06/2018
  • Caroline Campbell: 10/2016 - 06/2017
  • Douglas Bledsoe: 12/2015 -07/2018
  • Lucas Kane: 07/2013 -07/2015
Headshot of Blaise Costa.

After receiving a Pharmacy degree Blaise Costa pursued a theoretical biophysics research to study the structure, function and pharmacology of NMDA receptors that play a crucial role in learning and memory. For this work, he earned a PhD Degree in Psychopharmacology from The National Institute of Mental Health And Neurosciences, Bangalore India. To work out the theoretical findings, he undertook a molecular neuroscience training at the University of London. He won the Royal Society International award to fund this training. Subsequently, as a postdoc at Max Planck Institute for Brain Research, he further studied NMDA receptor function using electrophysiology techniques. To translate this knowledge into identification of novel therapeutic agents for brain disorders, he moved to the University of Nebraska Medical Center to work on a NIH funded project, for which he served as key personnel. During this work, his team discovered a novel family of negative and positive allosteric NMDA receptor modulators. These compounds are novel in their chemical structure, mechanism of action and binding sites. Currently, Costa lab is interested in identifying and developing NMDA receptor based therapeutic strategy for neurodegenerative disorders with a special focus on Alzheimer’s disease.

Download CV→

Biased NMDA Receptor Modulators and uses thereof. PCT/US2019/061308

Role: Inventor

Novel positive and negative allosteric aromatic ring modulators for composition of matter and methods of use. International publication number: WO2012/019106

Role: Co-inventor

View Pubmed publications list here.

Technical advancements in diagnosis and treatment of diseases necessitate highest standard of interdisciplinary approach in pharmacology curriculum. Most of the clinically used drugs bind with proteins (known as receptors) and cause conformational changes in their structure to activate or inactivate them to elicit clinically desirable effects. Medical students need to have a comprehensive understanding of this biophysico-chemical process perpetuated by the drugs that they would prescribe in the near future.

Teaching pharmacology provides a well-rounded understanding of biomedical sciences and helps to develop translational research programs. Blaise Costa is giving forty hours of pharmacology lectures to a class of 180 students. In the past five years, he received three golden apple awards by the Sigma Sigma Phi VCOM Chapter for the best teaching practices in biomedical sciences. 

GRA positions open periodically, interested candidates may send their CV to bcosta@vt.edu.

Virginia Tech Center for One Health Research

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