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Matthew D. Rand, Ph.D.

Contact Information

Phone Numbers

Appointment: (585) 276-3000

Research Labs

Faculty Appointments

Biography

Research

Neural developmental toxicity of methylmercury.

Dr. Rand's research focuses on the mechanisms of neural developmental toxicity of the persistent environmental toxin methylmercury (MeHg). Human exposure to MeHg through dietary intake of fish continues to be a major health concern. MeHg preferentially targets the developing nervous system leaving the fetus and young children at greatest risk from exposure.However, considerable uncertainty remains as to the risk of MeHg versus the benefit of essential nutrients in a fish diet. Further uncertainty stems from the wide range of inter-individual variability seen in neurological outcomes, both with MeHg-exposed laboratory animals and in human epidemiological studies of children in fish eating populations.

Our laboratory is engaged in several research projects elucidating molecular, cellular and genetic mechanisms of neural development responsible for variation in tolerance or susceptibility to MeHg toxicity. We are executing transcriptomic and genome wide association methods in the Drosophila model to elucidate fundamental genes that influence tolerance and susceptibility phenotypes in fruit flies developmentally exposed to MeHg. Assays are being conducted at the embryonic and larval/pupal developmental stages using functional assays that target transgenes to neural and non-neural tissues. Candidate genes from Phase I (Cytochrome p450), Phase II (Glutathione S-transferases, GCLm, GCLc) and Phase III (multidrug resistance like protein, MRP1, ABCC1) xenobiotic metabolism pathways have been identified, either through unbiased screens or prospective functional assays, as major effectors of MeHg tolerance and susceptibility. A role for these conventional metabolism genes, specifically in developing neurons, is being characterized. In addition, human homologs of these genes, carrying polymorphic variations known to associate with varied MeHg metabolism in people, are being functionally characterized in this Drosophila system. We are also investigating the role of dietary and nutritional supplements in modifying the MeHg effect in development. With this approach we have identified a protective function for caffeine, and are further investigating the potential protective mechanisms of vitamin E and selenium in MeHg toxicity.

Additional studies are exploiting a novel method developed in the lab to introduce acute doses of small molecules through the eggshell of viable Drosophila embryos. allow us to identify the most MeHg-sensitive window of neural development. These studies, together with studies investigating localization of MeHg in target organs of developing fruit fly larvae with X-Ray fluorescence imaging, are establishing the Drosophila model as a premier platform for basic research in toxicology. In addition, we are initiating studies to develop biomarkers and a protocol to determine MeHg metabolism rates in individual people. These latter studies are aimed at translating our functional studies of Phase I-III metabolism genes in MeHg toxicity to understanding the genetic basis of variation in MeHg susceptibility in populations and in individuals.

Credentials

Education

1986
B.S. | University of New Hampshire
Biology

1995
Ph.D. | University of Vermont, College of Medicine
Biochemistry

Post-doctoral Training & Residency

1998 - 2000
Research Fellow. Harvard Medical School, Cancer Center, Massachusetts General Hospital, Charlestown, MA. Advisor: Spyros Artavanis-Tsakonas, Ph.D. Research interests: Mechanisms of signal transduction in neurogenesis. Biochemical characterization of Notch receptor interaction with the Delta ligand. The role of the ADAM metalloprotease Kuzbanian in the proteolytic processing of the Notch ligands.

1997 - 1998
Research Fellow. Howard Hughes Medical Institute, Department of Cell Biology, Yale University School of Medicine, New Haven, CT. Advisor: Spyros Artavanis- Tsakonas, Ph.D. Research Interests: Interaction of the Notch receptor with its ligand Delta at the cellular level. Proteolytic processing of the Notch receptor and the Delta ligand.

1995 - 1997
Postdoctoral Fellowship. Department of Clinical Chemistry, Lund University, University Hospital, Malmo, Sweden. Advisor: Johan Stenflo, MD., Ph.D. Research Interests: Expression and characterization of tandem clacium-binding epidermal growth factor-like (EGF) modules from the ligand binding region of the human Notch receptor.

1991 - 1995
Doctoral Training- Department of Biochemistry, College of Medicine, University of Vermont, Burlington, VT. Advisor: Kenneth G. Mann, Ph.D. Research Interests: Phosphorylation of the coagulation cofactor factor Va by platelet kinasis. Characterization and determination of clearance rates of baboon factor V/Va. Development of a novel assay system to simultaneously quantitate activation of coagulation factors, inhibitor-enzyme complex formation and platelet activation during extrinsic pathway initiated clotting in whole blood.

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Awards

2011
UVM,"Inventor Hall of Fame"
Sponsor: For co-invention of a patent with successful commercialization
Location: Office of Technology Transfer, UVM- Burlington, VT.

Publications

Journal Articles

2/1/2018
Caito SW, Jackson BP, Punshon T, Scrimale T, Grier A, Gill SR, Love TM, Watson GE, van Wijngaarden E, Rand MD. "Editor's Highlight: Variation in Methylmercury Metabolism and Elimination Status in Humans Following Fish Consumption." Toxicological sciences : an official journal of the Society of Toxicology.. 2018 Feb 1; 161(2):443-453.

1/15/2018
Prince LM, Rand MD. "Methylmercury exposure causes a persistent inhibition of myogenin expression and C2C12 myoblast differentiation." Toxicology.. 2018 Jan 15; 393:113-122. Epub 2017 Nov 15.

8/2017
Llop S, Tran V, Ballester F, Barbone F, Sofianou-Katsoulis A, Sunyer J, Engström K, Alhamdow A, Love TM, Watson GE, Bustamante M, Murcia M, Iñiguez C, Shamlaye CF, Rosolen V, Mariuz M, Horvat M, Tratnik JS, Mazej D, van Wijngaarden E, Davidson PW, Myers GJ, Rand MD, Broberg K. "CYP3A genes and the association between prenatal methylmercury exposure and neurodevelopment." Environment international.. 2017 Aug 0; 105:34-42. Epub 2017 May 10.

Books & Chapters

2011
Chapter Title: Methylmercury Effects on Neural Developmental Signaling Pathways.
Book Title: Developmental Neurotoxicology Research: Principles, Models, Techniques, Strategi
Author List: Wand, C, and Slikker, W. Eds.
Published By: John Wiley & Sons., 2011. 2011

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