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Matthew D. Rand, Ph.D.

Matthew D. Rand, Ph.D.

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Environmental Health Sciences Center

Elemental Analysis Facility

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About Me

Faculty Appointments

Associate Professor - Department of Environmental Medicine (SMD)

Credentials

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. 1998 - 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. 1997 - 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 calcium-binding epidermal growth factor-like (EGF) modules from the ligand binding region of the human Notch receptor. 1995 - 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. 1991 - 1995

Education

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

B.S. | University of New Hampshire. Biology. 1986

Awards

UVM,"Inventor Hall of Fame". 2011

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 prefere...
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.

Publications

Journal Articles

Review: myogenic and muscle toxicity targets of environmental methylmercury exposure.

Tam LM, Rand MD

Archives of toxicology.. 2024 June 98 (6):1645-1658. Epub 03/28/2024.

Postnatal methylmercury exposure and neurodevelopmental outcomes at 7 years of age in the Seychelles Child Development Study Nutrition Cohort 2.

Klus JK, Thurston SW, Myers G, Watson GE, Rand MD, Love TM, Yeates AJ, Mulhern MS, McSorley EM, Strain JJ, Shamlaye C, van Wijngaarden E

Neurotoxicology.. 2023 December 99 :115-119. Epub 10/11/2023.

KEAP1 polymorphisms and neurodevelopmental outcomes in children with exposure to prenatal MeHg from the Seychelles Child Development Study Nutrition Cohort 2.

de Paula HK, Love TM, Pineda D, Watson GE, Thurston SW, Yeates AJ, Mulhern MS, McSorley EM, Strain JJ, Shamlaye CF, Myers GJ, Rand MD, van Wijngaarden E, Broberg K

Neurotoxicology.. 2023 December 99 :177-183. Epub 10/17/2023.

Assessing the role of the gut microbiome in methylmercury demethylation and elimination in humans and gnotobiotic mice.

Coe GL, Krout IN, Munro-Ehrlich M, Beamish CR, Vorojeikina D, Colman DR, Boyd EJ, Walk ST, Rand MD

Archives of toxicology.. 2023 September 97 (9):2399-2418. Epub 07/01/2023.

Perspectives on the Drosophila melanogaster Model for Advances in Toxicological Science.

Rand MD, Tennessen JM, Mackay TFC, Anholt RRH

Current protocols.. 2023 August 3 (8):e870. Epub 1900 01 01.

Targeted Intracellular Demethylation of Methylmercury Enhances Elimination Kinetics and Reduces Developmental Toxicity in Transgenic Drosophila.

Krout IN, Scrimale T, Rand MD

Toxicological sciences : an official journal of the Society of Toxicology.. 2022 November 23190 (2):146-157. Epub 1900 01 01.

Organomercurial Lyase (MerB)-Mediated Demethylation Decreases Bacterial Methylmercury Resistance in the Absence of Mercuric Reductase (MerA).

Krout IN, Scrimale T, Vorojekina D, Boyd ES, Rand MD

Applied and environmental microbiology.. 2022 March 2288 (6):e0001022. Epub 02/09/2022.

Delivery Mode and Child Development at 20 Months of Age and 7 Years of Age in the Republic of Seychelles.

Zavez A, Thurston SW, Rand MD, Mruzek DW, Love T, Smith T, Shamlaye CF, van Wijngaarden E

Maternal and child health journal.. 2021 December 25 (12):1930-1938. Epub 10/05/2021.

Neuroligin-1 Is a Mediator of Methylmercury Neuromuscular Toxicity.

Gunderson JT, Peppriell AE, Krout IN, Vorojeikina D, Rand MD

Toxicological sciences : an official journal of the Society of Toxicology.. 2021 November 24184 (2):236-251. Epub 1900 01 01.

Developmental Toxicology of Metal Mixtures in : Unique Properties of Potency and Interactions of Mercury Isoforms.

Beamish CR, Love TM, Rand MD

International journal of molecular sciences.. 2021 November 922 (22)Epub 11/09/2021.

Variation in Methylmercury Metabolism and Elimination in Humans: Physiological Pharmacokinetic Modeling Highlights the Role of Gut Biotransformation, Skeletal Muscle, and Hair.

Pope Q, Rand MD

Toxicological sciences : an official journal of the Society of Toxicology.. 2021 February 26180 (1):26-37. Epub 1900 01 01.

Associations of prenatal methylmercury exposure and maternal polyunsaturated fatty acid status with neurodevelopmental outcomes at 7 years of age: results from the Seychelles Child Development Study Nutrition Cohort 2.

Strain JJ, Love TM, Yeates AJ, Weller D, Mulhern MS, McSorley EM, Thurston SW, Watson GE, Mruzek D, Broberg K, Rand MD, Henderson J, Shamlaye CF, Myers GJ, Davidson PW, van Wijngaarden E

The American journal of clinical nutrition.. 2021 February 2113 (2):304-313. Epub 1900 01 01.

Associations of prenatal methylmercury exposure and maternal polyunsaturated fatty acid status with neurodevelopmental outcomes at 7 years of age: results from the Seychelles Child Development Study Nutrition Cohort 2.

Strain JJ, Love TM, Yeates AJ, Weller D, Mulhern MS, McSorley EM, Thurston SW, Watson GE, Mruzek D, Broberg K, Rand MD, Henderson J, Shamlaye CF, Myers GJ, Davidson PW, van Wijngaarden E

The American journal of clinical nutrition.. 2021 February 113 (2):304-313. Epub 1900 01 01.

Latent effects of early-life methylmercury exposure on motor function in Drosophila.

Peppriell AE, Gunderson JT, Krout IN, Vorojeikina D, Rand MD

Neurotoxicology and teratology.. 2021 88 :107037. Epub 10/14/2021.

Developmental exposure to methylmercury and resultant muscle mercury accumulation and adult motor deficits in mice.

Rand MD, Conrad K, Marvin E, Harvey K, Henderson D, Tawil R, Sobolewski M, Cory-Slechta DA

Neurotoxicology.. 2020 December 81 :1-10. Epub 07/28/2020.

Tissue-specific Nrf2 signaling protects against methylmercury toxicity in Drosophila neuromuscular development.

Gunderson JT, Peppriell AE, Vorojeikina D, Rand MD

Archives of toxicology.. 2020 December 94 (12):4007-4022. Epub 08/20/2020.

Methylmercury myotoxicity targets formation of the myotendinous junction.

Peppriell AE, Gunderson JT, Vorojeikina D, Rand MD

Toxicology.. 2020 October 443 :152561. Epub 08/13/2020.

Development of Human Hair Reference Material Supporting the Biomonitoring of Methylmercury.

Haraguchi K, Sakamoto M, Matsuyama A, Yamamoto M, Hung DT, Nagasaka H, Uchida K, Ito Y, Kodamantani H, Horvat M, Chan HM, Rand M, Cirtiu CM, Kim BG, Nielsen F, Yamakawa A, Mashyanov N, Panichev N, Panova E, Watanabe T, Kaneko N, Yoshinaga J, Herwati RF, Suoth AE, Akagi H

Analytical sciences : the international journal of the Japan Society for Analytical Chemistry.. 2020 May 1036 (5):561-565. Epub 03/06/2020.

Methylmercury modifies temporally expressed myogenic regulatory factors to inhibit myoblast differentiation.

Culbreth M, Rand MD

Toxicology in vitro : an international journal published in association with BIBRA.. 2020 March 63 :104717. Epub 11/06/2019.

Variation in the biological half-life of methylmercury in humans: Methods, measurements and meaning.

Rand MD, Caito SW

Biochimica et biophysica acta. General subjects.. 2019 December 1863 (12):129301. Epub 02/08/2019.

Associations of blood mercury and fatty acid concentrations with blood mitochondrial DNA copy number in the Seychelles Child Development Nutrition Study.

Xu Y, Wahlberg K, Love TM, Watson GE, Yeates AJ, Mulhern MS, McSorley EM, Strain JJ, Davidson PW, Shamlaye CF, Rand MD, Myers GJ, van Wijngaarden E, Broberg K

Environment international.. 2019 March 124 :278-283. Epub 01/17/2019.

Drosophotoxicology: Elucidating Kinetic and Dynamic Pathways of Methylmercury Toxicity in a Drosophila Model

Rand, MD; Vorojeikina, D; Peppriell, A; Gunderson, J; Prince, LM.

Front. Genet. 2019; .

Drosophotoxicology: Elucidating Kinetic and Dynamic Pathways of Methylmercury Toxicity in a Drosophila Model.

Rand MD, Vorojeikina D, Peppriell A, Gunderson J, Prince LM

Frontiers in genetics.. 2019 10 :666. Epub 08/09/2019.

Maternal polymorphisms in glutathione-related genes are associated with maternal mercury concentrations and early child neurodevelopment in a population with a fish-rich diet.

Wahlberg K, Love TM, Pineda D, Engström K, Watson GE, Thurston SW, Yeates AJ, Mulhern MS, McSorley EM, Strain JJ, Smith TH, Davidson PW, Shamlaye CF, Myers GJ, Rand MD, van Wijngaarden E, Broberg K

Environment international.. 2018 June 115 :142-149. Epub 03/21/2018.

Editor's Highlight: Variation in Methylmercury Metabolism and Elimination Status in Humans Following Fish Consumption.

Caito SW, Jackson BP, Punshon T, Scrimale T, Grier A, Gill SR, Love TM, Watson GE, van Wijngaarden E, Rand MD

Toxicological sciences : an official journal of the Society of Toxicology.. 2018 February 1161 (2):443-453. Epub 1900 01 01.

Methylmercury exposure causes a persistent inhibition of myogenin expression and C2C12 myoblast differentiation.

Prince LM, Rand MD

Toxicology.. 2018 January 15393 :113-122. Epub 11/15/2017.

CYP3A genes and the association between prenatal methylmercury exposure and neurodevelopment.

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

Environment international.. 2017 August 105 :34-42. Epub 05/10/2017.

Editor's Highlight: Glutathione S-Transferase Activity Moderates Methylmercury Toxicity During Development in Drosophila.

Vorojeikina D, Broberg K, Love TM, Davidson PW, van Wijngaarden E, Rand MD

Toxicological sciences : an official journal of the Society of Toxicology.. 2017 May 1157 (1):211-221. Epub 1900 01 01.

Notch Target Gene E(spl)m? Is a Mediator of Methylmercury-Induced Myotoxicity in .

Prince LM, Rand MD

Frontiers in genetics.. 2017 8 :233. Epub 01/15/2018.

Polymorphisms in ATP-binding cassette transporters associated with maternal methylmercury disposition and infant neurodevelopment in mother-infant pairs in the Seychelles Child Development Study.

Engström K, Love TM, Watson GE, Zareba G, Yeates A, Wahlberg K, Alhamdow A, Thurston SW, Mulhern M, McSorley EM, Strain JJ, Davidson PW, Shamlaye CF, Myers GJ, Rand MD, van Wijngaarden E, Broberg K

Environment international.. 2016 September 94 :224-229. Epub 06/02/2016.

Methods for Individualized Determination of Methylmercury Elimination Rate and De-Methylation Status in Humans Following Fish Consumption.

Rand MD, Vorojeikina D, van Wijngaarden E, Jackson BP, Scrimale T, Zareba G, Love TM, Myers GJ, Watson G

Toxicological sciences : an official journal of the Society of Toxicology.. 2016 February 149 (2):385-95. Epub 11/15/2015.

Target organ specific activity of drosophila MRP (ABCC1) moderates developmental toxicity of methylmercury.

Prince L, Korbas M, Davidson P, Broberg K, Rand MD

Toxicological sciences : an official journal of the Society of Toxicology.. 2014 August 1140 (2):425-35. Epub 05/25/2014.

A method of permeabilization of Drosophila embryos for assays of small molecule activity.

Rand MD

Journal of visualized experiments : JoVE.. 2014 July 13 (89)Epub 07/13/2014.

Developmental toxicity assays using the Drosophila model.

Rand MD, Montgomery SL, Prince L, Vorojeikina D

Current protocols in toxicology. 2014 February 1959 :1.12.1-20. Epub 02/19/2014.

The Notch target E(spl)m? is a muscle-specific gene involved in methylmercury toxicity in motor neuron development.

Engel GL, Rand MD

Neurotoxicology and teratology.. 2014 43 :11-8. Epub 03/13/2014.

Genome-wide association analysis of tolerance to methylmercury toxicity in Drosophila implicates myogenic and neuromuscular developmental pathways.

Montgomery SL, Vorojeikina D, Huang W, Mackay TF, Anholt RR, Rand MD

PloS one.. 2014 9 (10):e110375. Epub 10/31/2014.

Low level methylmercury enhances CNTF-evoked STAT3 signaling and glial differentiation in cultured cortical progenitor cells.

Jebbett NJ, Hamilton JW, Rand MD, Eckenstein F

Neurotoxicology.. 2013 September 38 :91-100. Epub 07/08/2013.

Drosophila CYP6g1 and its human homolog CYP3A4 confer tolerance to methylmercury during development.

Rand MD, Lowe JA, Mahapatra CT

Toxicology.. 2012 October 9300 (1-2):75-82. Epub 06/12/2012.

Methylmercury tolerance is associated with the humoral stress factor gene Turandot A.

Mahapatra CT, Rand MD

Neurotoxicology and teratology.. 2012 July 34 (4):387-94. Epub 04/24/2012.

The effects of methylmercury on Notch signaling during embryonic neural development in Drosophila melanogaster.

Engel GL, Delwig A, Rand MD

Toxicology in vitro : an international journal published in association with BIBRA.. 2012 April 26 (3):485-92. Epub 12/30/2011.

Permeabilization of Drosophila embryos for introduction of small molecules.

Rand MD, Kearney AL, Dao J, Clason T

Insect biochemistry and molecular biology.. 2010 November 40 (11):792-804. Epub 08/19/2010.

Identification of methylmercury tolerance gene candidates in Drosophila.

Mahapatra CT, Bond J, Rand DM, Rand MD

Toxicological sciences : an official journal of the Society of Toxicology.. 2010 July 116 (1):225-38. Epub 04/07/2010.

Drosophotoxicology: the growing potential for Drosophila in neurotoxicology.

Rand MD

Neurotoxicology and teratology.. 2010 32 (1):74-83. Epub 06/24/2009.

Methylmercury disruption of embryonic neural development in Drosophila.

Rand MD, Dao JC, Clason TA

Neurotoxicology.. 2009 September 30 (5):794-802. Epub 05/04/2009.

Methylmercury activates enhancer-of-split and bearded complex genes independent of the notch receptor.

Rand MD, Bland CE, Bond J

Toxicological sciences : an official journal of the Society of Toxicology.. 2008 July 104 (1):163-76. Epub 03/25/2008.

Kuz and TACE can activate Notch independent of ligand.

Delwig A, Rand MD

Cellular and molecular life sciences : CMLS.. 2008 July 65 (14):2232-43. Epub 1900 01 01.

Delta expression in post-mitotic neurons identifies distinct subsets of adult-specific lineages in Drosophila.

Cornbrooks C, Bland C, Williams DW, Truman JW, Rand MD

Developmental neurobiology.. 2007 January 67 (1):23-38. Epub 1900 01 01.

Methylmercury induces activation of Notch signaling.

Bland C, Rand MD

Neurotoxicology.. 2006 December 27 (6):982-91. Epub 04/28/2006.

Endocytosis-independent mechanisms of Delta ligand proteolysis.

Delwig A, Bland C, Beem-Miller M, Kimberly P, Rand MD

Experimental cell research.. 2006 May 1312 (8):1345-60. Epub 02/17/2006.

Notch-induced proteolysis and nuclear localization of the Delta ligand.

Bland CE, Kimberly P, Rand MD

The Journal of biological chemistry.. 2003 April 18278 (16):13607-10. Epub 02/18/2003.

Down-regulation of Delta by proteolytic processing.

Mishra-Gorur K, Rand MD, Perez-Villamil B, Artavanis-Tsakonas S

The Journal of cell biology.. 2002 October 28159 (2):313-24. Epub 10/28/2002.

Calcium depletion dissociates and activates heterodimeric notch receptors.

Rand MD, Grimm LM, Artavanis-Tsakonas S, Patriub V, Blacklow SC, Sklar J, Aster JC

Molecular and cellular biology.. 2000 March 20 (5):1825-35. Epub 1900 01 01.

Notch signaling: cell fate control and signal integration in development.

Artavanis-Tsakonas S, Rand MD, Lake RJ

Science.. 1999 April 30284 (5415):770-6. Epub 1900 01 01.

Processing of the notch ligand delta by the metalloprotease Kuzbanian.

Qi H, Rand MD, Wu X, Sestan N, Wang W, Rakic P, Xu T, Artavanis-Tsakonas S

Science.. 1999 January 1283 (5398):91-4. Epub 1900 01 01.

Calcium binding to tandem repeats of EGF-like modules. Expression and characterization of the EGF-like modules of human Notch-1 implicated in receptor-ligand interactions.

Rand MD, Lindblom A, Carlson J, Villoutreix BO, Stenflo J

Protein science : a publication of the Protein Society.. 1997 October 6 (10):2059-71. Epub 1900 01 01.

Blood clotting in minimally altered whole blood.

Rand MD, Lock JB, van't Veer C, Gaffney DP, Mann KG

Blood.. 1996 November 188 (9):3432-45. Epub 1900 01 01.

Factor V turnover in a primate model.

Rand MD, Hanson SR, Mann KG

Blood.. 1995 October 186 (7):2616-23. Epub 1900 01 01.

Factor VNew Brunswick: Ala221-to-Val substitution results in reduced cofactor activity.

Murray JM, Rand MD, Egan JO, Murphy S, Kim HC, Mann KG

Blood.. 1995 September 186 (5):1820-7. Epub 1900 01 01.

Characterization of the molecular defect in factor VR506Q.

Kalafatis M, Bertina RM, Rand MD, Mann KG

The Journal of biological chemistry.. 1995 February 24270 (8):4053-7. Epub 1900 01 01.

The mechanism of inactivation of human factor V and human factor Va by activated protein C.

Kalafatis M, Rand MD, Mann KG

The Journal of biological chemistry.. 1994 December 16269 (50):31869-80. Epub 1900 01 01.

Membrane-dependent reactions in blood coagulation: role of the vitamin K-dependent enzyme complexes.

Kalafatis M, Swords NA, Rand MD, Mann KG

Biochimica et biophysica acta.. 1994 November 291227 (3):113-29. Epub 1900 01 01.

Platelet coagulation factor Va: the major secretory platelet phosphoprotein.

Rand MD, Kalafatis M, Mann KG

Blood.. 1994 April 1583 (8):2180-90. Epub 1900 01 01.

Factor Va-membrane interaction is mediated by two regions located on the light chain of the cofactor.

Kalafatis M, Rand MD, Mann KG

Biochemistry.. 1994 January 1833 (2):486-93. Epub 1900 01 01.

Phosphorylation of factor Va and factor VIIIa by activated platelets.

Kalafatis M, Rand MD, Jenny RJ, Ehrlich YH, Mann KG

Blood.. 1993 February 181 (3):704-19. Epub 1900 01 01.

Factor V.

Kalafatis M, Krishnaswamy S, Rand MD, Mann KG

Methods in enzymology.. 1993 222 :224-36. Epub 1900 01 01.

Books

Developmental Neurotoxicology Research: Principles, Models, Techniques, Strategi (2011)

Chapter: Methylmercury Effects on Neural Developmental Signaling Pathways.

Authors: Wand, C, and Slikker, W. Eds.

Publisher: John Wiley & Sons., 2011. 2011