Matthew D. Rand, Ph.D.

Matthew D. Rand, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box EHSC
Rochester, NY 14642

Research Bio

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.

Awards & Honors (Local)

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

Recent Journal Articles

Showing the 5 most recent journal articles. 29 available »

2013 Sep
Jebbett NJ, Hamilton JW, Rand MD, Eckenstein F. "Low level methylmercury enhances CNTF-evoked STAT3 signaling and glial differentiation in cultured cortical progenitor cells." Neurotoxicology.. 2013 Sep; 38:91-100. Epub 2013 Jul 08.
2012 Oct 9
Rand MD, Lowe JA, Mahapatra CT. "Drosophila CYP6g1 and its human homolog CYP3A4 confer tolerance to methylmercury during development." Toxicology.. 2012 Oct 9; 300(1-2):75-82. Epub 2012 Jun 12.
2012 Jul
Mahapatra CT, Rand MD. "Methylmercury tolerance is associated with the humoral stress factor gene Turandot A." Neurotoxicology and teratology.. 2012 Jul; 34(4):387-94. Epub 2012 Apr 24.
2012 Apr
Engel GL, Delwig A, Rand MD. "The effects of methylmercury on Notch signaling during embryonic neural development in Drosophila melanogaster." Toxicology in vitro : an international journal published in association with BIBRA. 2012 Apr; 26(3):485-92. Epub 2011 Dec 30.
2010 Nov
Rand MD, Kearney AL, Dao J, Clason T. "Permeabilization of Drosophila embryos for introduction of small molecules." Insect biochemistry and molecular biology. 2010 Nov; 40(11):792-804. Epub 2010 Aug 19.

Current Appointments

Assistant Professor - Department of Environmental Medicine (SMD) - Primary

Education

Ph.D. | Biochemistry | University of Vermont, College of Medicine1995
B.S. | Biology | University of New Hampshire1986

Post-Doctoral Training & Residency

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. 2000
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. 1998
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. 1997
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. 1995