College of Nursing and Health Sciences

The Department of Biomedical and Health Sciences

Krementsov Lab

Dimitry Krementsov looks through microscope

Research

Research in the Krementsov laboratory is focused on understanding the molecular mechanisms underlying the pathogenesis of immune-mediated or infectious diseases. One of our principal interests is the autoimmune disease multiple sclerosis (MS), the most common neurologic disorder affecting young adults, which occurs when the immune system aberrantly initiates an attack against the central nervous system.

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The etiology of chronic autoimmune diseases, such as MS, is complex and multifactorial, dictated by genetic and environmental risk factors. The mechanisms and interplay of these risk factors are difficult to determine in human studies. Research in the Krementsov lab applies unique mouse genetics approaches to assess the role of genes and environment in MS and other immune-mediated diseases. A major current focus is unraveling the complex interactions between host genetics and the gut microbiome, as a novel putative risk factor for many chronic diseases.

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MS is three times more prevalent in women, but more severe in men, and our research is also aimed at understanding why and how MS affects women and men differently. This line of investigation has uncovered a druggable molecular pathway in macrophages and microglia, which is regulated by estrogen.

Other interests in the lab include genetics of other immune-mediated diseases such as inflammatory bowel disease, as well as genetics of host-pathogen interactions, especially viruses. We employ various immunologic and molecular techniques, animal and cellular models, as well as genomic approaches.

Principal Investigator

Dimitry N. Krementsov, Assistant Professor, Department of Biomedical and Health Sciences

Dimitry was initially trained as a molecular biologist, later picking up virology, immunology, and a bit of genetics along the way. He believes that biology makes the most sense when viewed through the lens of evolution (Dobzhansky, 1973). In addition to research, Dimitry is passionate about teaching at the undergraduate and graduate levels. Learn more >>

Lab Members

Staff

Karrie Lahue, senior laboratory technician and lab manager, Karrie.Lahue@uvm.edu

Karrie received her bachelor's in Biochemistry from St. Michael's College, and has been working at UVM for well over a decade. Serendipitously joining the Krementsov lab at its inception, she first worked on modeling genetics of IBD susceptibility. Her current focus has been implementing a mouse model of MS to investigate genetic risk factors. Research endeavors aside, she ventures to lend a hand to everyone and cheerfully fulfills her self-professed epithet of "lab mom" by baking and generally attempting to maintain a lab culture of contentment.

Benjamin Liebman, laboratory technician, Benjamin.Liebman@med.uvm.edu

Ben received his B.A. in molecular biology and biochemistry from Hampshire College and his M.S. in pharmacology from the University of Vermont. His recent graduate work centered on harnessing the paracrine activity of growth factor/immunoglobulin complexes to treat ischemic tissue injury in pigs. His current work in the Krementsov lab is aimed at understanding the importance of microglial inflammatory phenotypes in Alzheimer’s disease progression.

Ph.D. Students

"Bristy" Sabikunnahar, M.S., CMB program, Sabikunnahar@uvm.edu

Bristy got her B.S. and M.S. from University of Dhaka, Bangladesh, prior to moving across the world to pursue her Ph.D. studies in Vermont. Bristy is exploring the role of a novel lncRNA in myeloid cell function. She is highly valued in the lab because of her collaborative spirit and supreme cooking ability, including a highly sought-after chicken biryani.

Theresa Montgomery, B.S., CMB program, Theresa.Montgomery@uvm.edu

Theresa got her B.S. from UVM and spent several years afterwards there as a technician working on viral immunology, before joining the CMB program. She currently works on host-microbiome interactions in autoimmune disease, and is particularly skilled in isolation and anaerobic culture of gut bacteria.

Emily Holt, B.S., CMB program, Emily.A.Holt@uvm.edu

A UVM graduate, Emily is currently working on modeling genetic heterogeneity in MS using Collaborative Cross mice, as well as identifying genetic interactions with gammaherpes virus infection as a risk factor for MS.

Dan Peipert, B.S., NGP program, dpeipert@uvm.edu

Dan received his B.S. in neuroscience from UVM. He then worked as a research assistant at Dartmouth studying environmental risk factors for ALS. Upon returning to UVM for his Ph.D., he joined the Krementsov lab, where he is investigating the role of the specific gut commensal microbes in mouse models of MS.

Undergraduate Researchers

Sydney Caldwell, MMG

Sydney is studying the novel long non-coding RNA U90926 and its potential effects on adipogenesis in vivo, specifically its role in the regulation of adipocytes, adipose tissue macrophages, and other immune cells.

Eamonn Heney, Biology

Eamonn is studying the role of the commensal gut bacteria in models of multiple sclerosis.

Former Lab Members

Stella Varnum, B.S. in Biochemistry, 2021

Current position: Ph.D. program in Immunology, University of Washington in St. Louis

Lorrie Blais, M.S. in MLS, 2021

Current position: Vermont Department of Health Labs

Mahalia McGill, laboratory technician, 2021-2021

Current position: Field Application Specialist, Biotek/Agilent

Josie Kennedy, undergraduate researcher, MLS 2020

Current position: Medical Laboratory Scientist, MGH

Grace Voorhees, M.S. in Pharmacology student, 2019

Current position: Senior research associate at Cygnal Therapeutics

Alexei (Rachel) Cooper, Laboratory Technician, 2017-2018.

Current position: PhD program in MCB at UConn

Lab Highlights

News

August 2021 – welcome to the newest DK lab members, Dan Peipert, Benjamin Liebman, and Eamonn Heney! Sad goodbyes to Mahalia, Lorrie, and Stella!

July 2021 – Lorrie’s (unofficially systematic, and certainly comprehensive) review is now published in Gut Microbes. A labor of love!

June 2021 – Our report on unintentional contamination of lab personnel by SARS-CoV-2 DNA plasmids causing false positive RT-PCR surveillance is now published in J Clin Micro. Special thanks to Drs. Jess Crothers and Michelle Paavola for their efforts on this.

November 2020 – Several lay press features are published highlighting Theresa’s microbiome paper. Here is one.

November 2020 – 2 papers published: Karrie and Montana’s paper on genetics of IBD in Genes and Immunity, and Theresa’s paper on microbiome in a mouse model of MS, in PNAS !

May 2020 - Welcome to our newest PhD candidate, Emily Holt!

March-May 2020 – During the COVID-19 University shutdown, Karrie, Mahalia, Theresa, and Bristy stay on the frontline to keep essential activities in the lab running!

March 2020 – Mahalia and Bristy’s paper published in Journal of Neuroimmunology

December 2019 – Theresa invited to participate in the ACTRIMS Young Scientist Summit to be held January 2020 in Austin, Texas

Fall 2019 – The NIAID and National MS Society co-fund our new approach to mapping the genetic basis of MS disease course heterogeneity using a new systems genetics approach – the Collaborative Cross

August 2019 – Theresa appointed to the VCIID T32 training grant

June 2019 – M.S. candidate Grace Voorhees successfully defends her Master's Thesis, making her the first DK lab graduate!

May 2019 – four members of the lab present at the 2019 American Association of Immunologists Annual Meeting in San Diego. Theresa selected for oral presentation and trainee abstract award

May 2018 – welcome to two new Ph.D. candidates: Bristy Sabikunnahar and Theresa Montgomery!

December 2017 – Krementsov lab finally moves into their newly renovated space in Rowell!

August 2017 – Dimitry begins his new appointment in the Department of Biomedical and Health Sciences.

Selected Recent Publications

Full Bibliography on Pubmed

2023

Sabikunnahar B, Caldwell S, Varnum S, Hogan T, Cooper A, Lahue KG, Bivona JJ, Cousens PM, Symeonides M, Ballif BA, Poynter ME, Krementsov DN. Long Noncoding RNA U90926 Is Induced in Activated Macrophages, Is Protective in Endotoxic Shock, and Encodes a Novel Secreted Protein. J Immunol. 2023 Jan 27:ji2200215. doi: 10.4049/jimmunol.2200215. Epub ahead of print. PMID: 36705532.

2022

Montgomery TL, Eckstrom K, Lile KH, Caldwell S, Heney ER, Lahue KG, D'Alessandro A, Wargo MJ, Krementsov DN. Lactobacillus reuteri tryptophan metabolism promotes host susceptibility to CNS autoimmunity. Microbiome. 2022 Nov 23;10(1):198. doi: 10.1186/s40168-022-01408-7. PubMed PMID: 36419205.

Sabikunnahar B, Lahue KG, Asarian L, Fang Q, McGill MM, Haynes L, Teuscher C, Krementsov DN. Sex differences in susceptibility to influenza A virus infection depend on host genotype. PLoS One. 2022;17(9):e0273050. doi: 10.1371/journal.pone.0273050. eCollection 2022. PubMed PMID: 36112601.

Snyder, J. P., S. K. Gullickson, R. del Rio-Guerra, A. Sweezy, B. Vagher, T. C. Hogan, K. G. Lahue, J. A. Reisz, A. D’Alessandro, D. N. Krementsov*, and E. Amiel*. 2022. Divergent genetic regulation of nitric oxide production between C57BL/6J and wild-derived PWD/PhJ mice controls postactivation mitochondrial metabolism, cell survival, and bacterial resistance in dendritic cells. J Immunol. 2022 Jan 1;208(1):97-109. doi: 10.4049/jimmunol.2100375. Epub 2021 Dec 6. PubMed PMID: 34872978 *denotes co-senior author contribution.

2021

Montgomery TL, Paavola M, Bruce EA, Botten JW, Crothers JW, Krementsov DN. Laboratory worker self-contamination with non-infectious SARS-CoV-2 DNA can result in false positive RT-PCR-based surveillance testing. J Clin Microbiol. 2021 Jun 18;59(7):e0072321. doi: 10.1128/JCM.00723-21. Epub 2021 Jun 18. PMID: 33952597.

Blais LL, Montgomery TL, Amiel E, Deming PB, Krementsov DN. Probiotic and commensal gut microbial therapies in multiple sclerosis and its animal models: a comprehensive review. Gut Microbes. 2021 Jan-Dec;13(1):1943289. doi: 10.1080/19490976.2021.1943289. PMID: 34264791

2020

Montgomery T, Künstner A, Kennedy JJ, Fang Q, Asarian L, Culp-Hill R, D’Alessandro A, Teuscher C, Busch H, Krementsov DN. Interactions between host genetics and gut microbiota determine susceptibility to CNS autoimmunity. Proc Natl Acad Sci U S A. 2020 Oct 19;202002817. View commentary on the article >>

Lahue KG, Lara MK, Linton AA, Lavoie B, Fang Q, McGill MM, Crothers JW, Teuscher C, Mawe GM, Tyler AL, Mahoney JM, Krementsov DN. Identification of novel loci controlling inflammatory bowel disease susceptibility utilizing the genetic diversity of wild-derived mice. Genes and Immunity. (2020).

McGill MM, Sabikunnahar B, Fang Q, Teuscher C, Krementsov DN. The sex-specific role of p38 MAP kinase in CNS autoimmunity is regulated by estrogen receptor alpha. J Neuroimmunol. 2020 Mar 4;342:577209.

2019

Tyler AL, Raza A, Krementsov DN, Case LK, Huang R, Ma RZ, Blankenhorn EP, Teuscher C, Mahoney JM. Network-Based Functional Prediction Augments Genetic Association To Predict Candidate Genes for Histamine Hypersensitivity in Mice. G3 (Bethesda). 2019 Dec 3;9(12):4223-4233.

Raza A, Xie Z, Chan EC, Chen WS, Scott LM, Robin Eisch A, Krementsov DN, Rosenberg HF, Parikh SM, Blankenhorn EP, Teuscher C, Druey KM. A natural mouse model reveals genetic determinants of systemic capillary leak syndrome (Clarkson disease). Commun Biol. 2019 Oct 31;2(1):398.

2018

Krementsov DN, Asarian L, Fang Q, McGill MM, Teuscher C. Sex-Specific Gene-by-Vitamin D Interactions Regulate Susceptibility to Central Nervous System Autoimmunity. Front Immunol. 2018 Jul 17;9:1622. doi:10.3389/fimmu.2018.01622. PMID: 30065723

Boisson-Dupuis S, Ramirez-Alejo N, Li Z, Patin E, Rao G, Kerner G, Lim CK, Krementsov DN, et al. …Abel L, Casanova JL. Tuberculosis and impaired IL-23-dependent IFN-γ immunity in humans homozygous for a common TYK2 missense variant. Sci Immunol. 2018 Dec 21;3(30). pii: eaau8714.

2017

Raza A, Crothers JW, McGill MM, Mawe GM, Teuscher C, Krementsov DN. Anti-inflammatory roles of p38α MAPK in macrophages are context dependen t and require IL-10. J Leukoc Biol. 2017 Nov;102(5):1219-1227.

Krementsov DN, Case LK, Dienz O, Raza A, Fang Q, Ather JL, Poynter ME, Boyson JE, Bunn JY, Teuscher C. Genetic variation in chromosome Y regulates susceptibility to influenza A virus infection. Proc Natl Acad Sci U S A. 2017 Feb 27. pii: 201620889. Highlighted on the cover of PNAS, on This Week in Virology, and on Virology Blog

2016

Bearoff F, del Rio R, Case LK, Dragon JA, Nguyen-Vu T, Lin CY, Blankenhorn EP, Teuscher C, Krementsov DN. Natural genetic variation profoundly regulates gene expression in immune cells and dictates susceptibility to CNS autoimmunity. Genes and Immunity 2016 Dec;17(7):386-395. doi:10.1038/gene.2016.37. PMID: 27653816

Funding

The Krementsov Lab receives funding from the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases, the National Multiple Sclerosis Society, and the NIH National Institute of Neurological Disorders and Stroke.

CONTACT

Dimitry N. Krementsov

Assistant Professor

Dept. of Biomedical and Health Sciences

Dimitry.Krementsov@uvm.edu