Research staff:
Laura Cort, instructor
Frank Bearoff, PhD, postdoctoral fellow

Graduate students:
Andrew Heinemann, MLAS candidate
Marcus Willis, MLAS candidate

The goal of the research in our laboratory is to understand the genetic basis for inherited susceptibility to viral infections and to autoimmune diseases, including diabetes, scleroderma and multiple sclerosis. We also have a long-standing interest in the genetic architecture of ALS. In our work, backcross and F2 progeny are screened for alleles at many genetic loci. The inheritance of these alleles is compared to the inheritance of the phenotype (“linked”) and a preliminary assignment of the location of incidence and quantitative trait loci (QTL) is made. The QTL are confirmed in subsequent crosses, or are fixed in the genome by selective breeding, for positional cloning and identification of the disease gene itself.

Dr. Blankenhorn’s laboratory group usually consists of one to two research assistants and one to three graduate students. She maintains grant funding for several projects. Current grants include: two grants on the genetics of amyotrophic lateral sclerosis (ALS) in a mouse model, one with Dr. Terry Heiman-Paterson, now of Temple University, as PI and one with Dr. Heiman-Patterson as co-I, from the ALS Association. Dr. Blankenhorn is PI on a CURE grant with Dr. Hao Cheng of the College of Engineering on the topic of “Tolerance-Inducing Scaffolds for Treatment of a Multiple Sclerosis Model,” and has several grant applications in with him on this topic. She and Dr. Cheng were awarded an NIH R21 grant on similar research. She is PI of an NIH R21 grant on finding the gene on chromosome 10 that controls susceptibility to the mouse model of multiple sclerosis. She is also the PI on the Drexel subcontract from University of Massachusetts for an American Diabetes Association award (2016-2018) entitled “Preventing type 1 diabetes by targeting the causative T cell subset.”

We currently have several projects underway, including studies to examine the genetic control and the sexual dimorphism of susceptibility to mouse experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis. As noted above, we are also leading a project on the influence of non-coding genetic loci called single nucleotide polymorphisms (SNP) on the inherited component of human type I diabetes.

Selected Publications
(See all Elizabeth Blankenhorn's publications in PubMed.)

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

Identification of Optimal Mouse Models of Systemic Sclerosis by Interspecies Comparative Genomics
Sargent JL, Li Z, Aliprantis AO, Greenblatt M, Lemaire R, Wu MH, Wei J, Taroni J, Harris A, Long KB, Burgwin C, Artlett CM, Blankenhorn EP, Lafyatis R, Varga J, Clark SH, Whitfield ML
Arthritis Rheumatol.;68(8):2003-15. doi: 10.1002/art.39658, August 2016

Copy number variation in Y chromosome multicopy genes is linked to a paternal parent-of-origin effect on CNS autoimmune disease in female offspring
Case LK, Wall EH, Osmanski EE, Dragon JA, Saligrama N, Zachary JF, Lemos B, Blankenhorn EP, Teuscher C
Genome Biol.;16:28. doi: 10.1186/s13059-015-0591-7, Feb 10, 2015

Genetic background effects on disease onset and lifespan of the mutant dynactin p150Glued mouse model of motor neuron disease
Heiman-Patterson TD, Blankenhorn EP, Sher RB, Jiang J, Welsh P, Dixon MC, Jeffrey JI, Wong P, Cox GA, Alexander GM
PLoS One;10(3):e0117848. doi: 10.1371/journal.pone.0117848, Mar 12, 2015

Identification of genetic determinants of the sexual dimorphism in CNS autoimmunity
Bearoff F, Case LK, Krementsov DN, Wall EH, Saligrama N, Blankenhorn EP, Teuscher C
PLoS One;10(2):e0117993. doi: 10.1371/journal.pone.0117993, Feb 11, 2015

The Tsk2/+ mouse fibrotic phenotype is due to a gain-of-function mutation in the PIIINP segment of the Col3a1 gene
Long KB, Li Z, Burgwin CM, Choe SG, Martyanov V, Sassi-Gaha S, Earl JP, Eutsey RA, Ahmed A, Ehrlich GD, Artlett CM, Whitfield ML, Blankenhorn EP
J Invest Dermatol.;135(3):718-27. doi: 10.1038/jid.2014.455, Mar 2015

Tight Skin 2 Mice Exhibit Delayed Wound Healing Caused by Increased Elastic Fibers in Fibrotic Skin
Long KB, Burgwin CM, Huneke R, Artlett CM, Blankenhorn EP
Adv Wound Care (New Rochelle);3(9):573-581, Sep 1, 2014

Inflammation, Healing, and Genes: A Preface
Heber-Katz E, Blankenhorn EP
Adv Wound Care (New Rochelle);3(9):561-562, Sep 1, 2014

Tight skin 2 mice exhibit a novel time line of events leading to increased extracellular matrix deposition and dermal fibrosis
Long KB, Artlett CM, Blankenhorn EP
Matrix Biol.;38:91-100. doi: 10.1016/j.matbio.2014.05.002, Sep 2014

Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line
Cheverud JM, Lawson HA, Bouckaert K, Kossenkov AV, Showe LC, Cort L, Blankenhorn EP, Bedelbaeva K, Gourevitch D, Zhang Y, Heber-Katz E
Heredity (Edinb);112(5):508-18. doi: 10.1038/hdy.2013.133, May 2014

Diubiquitin (Ubd) is a susceptibility gene for virus-triggered autoimmune diabetes in rats
Cort L, Habib M, Eberwine RA, Hessner MJ, Mordes JP, Blankenhorn EP
Genes Immun.;15(3):168-75. doi: 10.1038/gene.2013.72, Apr-May 2014

Autoantigen-induced focusing of Vβ13+ T cells precedes onset of autoimmune diabetes in the LEW.1WR1 rat
Eberwine RA, Cort L, Habib M, Mordes JP, Blankenhorn EP
Diabetes;63(2):596-604. doi: 10.2337/db13-0462, Feb 2014

Histamine H(3) receptor integrates peripheral inflammatory signals in the neurogenic control of immune responses and autoimmune disease susceptibility
Krementsov DN, Wall EH, Martin RA, Subramanian M, Noubade R, Del Rio R, Mawe GM, Bond JP, Poynter ME, Blankenhorn EP, Teuscher C
PLoS One;8(7):e62743. doi: 10.1371/journal.pone.0062743, Jul 22, 2013

The Y chromosome as a regulatory element shaping immune cell transcriptomes and susceptibility to autoimmune disease
Case LK, Wall EH, Dragon JA, Saligrama N, Krementsov DN, Moussawi M, Zachary JF, Huber SA, Blankenhorn EP, Teuscher C
Genome Res.;23(9):1474-85. doi: 10.1101/gr.156703.113, Sep 2013

Temporal induction of immunoregulatory processes coincides with age-dependent resistance to viral-induced type 1 diabetes
Chen YG, Mordes JP, Blankenhorn EP, Kashmiri H, Kaldunski ML, Jia S, Geoffrey R, Wang X, Hessner MJ
Genes Immun.;14(6):387-400. doi: 10.1038/gene.2013.31, Sep 2013

The Missing Heritability in T1D and Potential New Targets for Prevention
Pierce BG, Eberwine R, Noble JA, Habib M, Shulha HP, Weng Z, Blankenhorn EP, Mordes JP
J Diabetes Res.;2013:737485. doi: 10.1155/2013/737485, 2013

Prevention of type 1 diabetes in the rat with an allele-specific anti-T-cell receptor antibody: Vβ13 as a therapeutic target and biomarker
Liu Z, Cort L, Eberwine R, Herrmann T, Leif JH, Greiner DL, Yahalom B, Blankenhorn EP, and JP Mordes
Diabetes, 61(5): 1160-1168, 2012

Genetics of EAE Supports the Role of T Helper Cells in MS Pathogenesis
Blankenhorn EP, Butterfield R, Case LK, Wall EH, del Rio R, Diehl SA, Krementsov D, Saligrama N, and C Teuscher
Ann. Neurol., 70(6): 887-896, 2011

Multiple linked quantitative trait loci within the Tmevd2/Eae3 interval control the severity of experimental allergic encephalomyelitis in DBA/2J mice. Spach KM, Case LK, Noubade R, Petersen CB, McElvany B, Zalik N, Hickey WF, Blankenhorn EP, and C Teuscher Genes and Immunity, 11(8): 649-659, 2010.

The postnatal maternal environment affects autoimmune disease susceptibility in A/J mice
Case LK, Del Rio R, Bonney EA, Zachary JF, Blankenhorn EP, Tung KS, and C Teuscher
Immunology & Cell Biology 260(2): 119-127, 2010

Infection with viruses from several families triggers autoimmune diabetes in LEW.1WR1 rats: prevention of diabetes by maternal immunization
Tirabassi RS, Guberski DL, Blankenhorn EP, Leif JH, Woda BA, Liu Z, Winans D, Greiner DL, and JP Mordes
Diabetes, 59(1): 110-118, 2009

A single nucleotide polymorphism in Tyk2 controls susceptibility to experimental allergic encephalomyelitis
Spach KM, Noubade R, McElvany B, Hickey WF, Blankenhorn EP, and C Teuscher
The Journal of Immunology, 182(12): 7776-7783, 2009

Cutting edge: The Y chromosome controls the age-dependent experimental allergic encephalomyelitis sexual dimorphism in SJL/J mice
Spach KM, Blake M, Bunn JY, McElvany B, Noubade R, Blankenhorn EP, an C Teuscher
The Journal of Immunology, 182: 1789-1793, 2009

Analysis of the rat Iddm14 diabetes susceptibility locus in multiple rat strains: identification of a susceptibility haplotype in the Tcrb-V  locus
Mordes JP, Cort L, Norowski E, Leif J, Fuller JM, Lernmark A, Greiner DL, and EP Blankenhorn
Mammalian Genome (3): 162-169, 2009

Virus-induced autoimmune diabetes in the LEW.1WR1 rat requires Iddm14 and a locus proximal to the major histocompatibility complex
Blankenhorn EP, Cort L, Greiner DL, Guberski DL, and JP Mordes
Diabetes, 58: 2930-2938, 2009

Genetic loci that regulate healing and regeneration in LG/J and SM/J mice
Blankenhorn EP, Bryan G, Kossenkov AV, Clark LD, Zhang XM, Chang C, Horng W, Pletscher LS, Cheverud JM, Showe LC, and E Heber-Katz
Mamm. Genome, 20: 720-733. 2009

Central histamine H3 receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS
Teuscher C, Subramanian M, Noubade R, Gao JF, Offner H, Zachary JF, and EP Blankenhorn
Proceedings of the National Academy of Sciences of the United States of America, 104(24): 10146-10151, 2007

Histamine receptor H1 is required for TCR-mediated p38 MAPK activation and optimal IFN-gamma production in mice
Noubade R, Milligan G, Zachary JF, Blankenhorn EP, del Rio R, Rincon M, and C Teuscher
Journal of Clinical Investigation 117(11): 3507-3518, 2007

Evidence that the Y-Chromosome influences EAE in male and female mice
Teuscher C, Noubade R, Spach K, Bunn JY, Fillmore PD, Zachary JF, and EP Blankenhorn
Proceedings of the National Academy of Sciences. 103: 8024-8029, 2006

The complex Trait Consortium.  The nature and identification of quantitative trait loci: a community's view
Abiola O, Angel JM, Avner P, Bachmanov AA, Belknap JK, Bennett B, Blankenhorn EP
Nature Reviews Genetics, 4: 911-916, 2003

Identification of Bphs, an Autoimmune Disease Locus, as Histamine Receptor H1
Ma RZ, Gao J, Meeker ND, Fillmore PD, Tung KSK, WatanabeT, Zachary JF, Offner H, Blankenhorn EP, and C Teuscher
Science, 297: 620-623, 2002