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Education and Training:

B.A., Microbiology, Miami University, Oxford, OH (1990-94)

M.D., Case Western Reserve University, School of Medicine, Cleveland, OH (1994-98)

Intern/Resident (Internal Medicine Accelerated Residency), University Hospitals of Cleveland, Cleveland, OH (1997-00)

Fellow, Hematology/Oncology, University of Michigan, Ann Arbor, Michigan (2000-03)

Lecturer/Post-doctoral Research Fellow, Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan (2003-07)

Jill Johnsen, M.D.
Assistant Professor of Medicine, Division of Hematology
University of Washington School of Medicine

Assistant Member
Puget Sound Blood Center Research Institute
Office Address:
Puget Sound Blood Center
Box 359190
1551 Eastlake Avenue E, Suite 100
Seattle, WA 98102

Phone: (206) 568-2230; 
Rachel Sessum: (206) 568-2246
Fax:     (206) 587-6056
E-mail:  jjohnsen@uw.edu
Johnsen Lab:  http://www.psbc.org/research/johnsen.htm

CURRENT CLINICAL INTERESTS

Disorders of hemostasis and thrombosis, VWD, ITP, blood group systems


CURRENT RESEARCH INTERESTS

Modifiers of von Willebrand Factor (VWF), von Willebrand Diseases (VWD), vascular endothelial gene expression, familial ITP, pregnancy-related hematologic disorders, glycan-mediated host-microbe interactions, blood group antigens


RESEARCH DESCRIPTION

The regulation of endothelial cell gene expression plays a central role in maintaining hemostatic balance, and we do not yet fully understand the key sequence elements responsible for the control of the endothelial gene expression program.  The inbred mouse strain, RIIIS/J, was found to have an endothelial-specific regulatory mutation in the gene encoding an N-acetylgalactosaminyltransferase, B4GALNT2.  This regulatory mutation, termed Mvwf1, directs a tissue-specific switch in the B4galnt2 gene expression program from intestinal epithelium to vascular endothelium. The endothelial expression of B4GALNT2 results in aberrant glycosylation of von Willebrand Factor (VWF) and accelerated VWF clearance from circulation, causing a phenotype very similar to Type 1 von Willebrand Disease (VWD) in humans.   We are now using a variety of molecular techniques to characterize the mechanism underlying this unique tissue-specific switch in gene expression.

The Mvwf1 allele exists in some contemporary wild mouse populations, where there are striking signatures of selection at the B4galnt2 locus.  We are studying the evolution of this allele in the genus Mus, where we have found strong evidence of long-term balancing selection.  In addition to the role VWF could play in the maintenance of Mvwf1 in natural populations, we hypothesize that a favorable phenotype may be conferred to wild mice by loss of B4galnt2 bowel expression.  We are now exploring the interaction of microbes with B4galnt2-sugars and other carbohydrate blood groups (H and ABO) at the mucosal surface.

Levels of the clotting protein, von Willebrand Factor (VWF), increase during pregnancy and likely play a role in the significantly increase in risk of clotting observed during pregnancy and in the post-partum period.  The life-threatening pregnancy-related disorders pre-eclampsia/eclampsia and HELLP exhibit even higher levels of VWF.  We are studying VWF changes during normal pregnancy, and plan to expand these studies to complicated pregnancies with the goal of developing diagnostic tools or identifying novel therapeutic targets for pregnancy-related disorders of hemostasis and thrombosis.

The human orthologue of the glycosyltransferase B4galnt2 confers the minor blood group antigen, Sda.  Other carbohydrate blood group antigens have been implicated in altering VWF levels and possibly influencing risk for thrombosis and bleeding.  We are taking a genetic approach to understand the biological significance of VWF glycosylation patterns by blood group glycosyltransferases, including Sda, ABO,and H.

Blood group antigens exhibit considerable diversity in human populations.  We seek to deeply characterize the genetic diversity underlying blood group variation and to correlate these variants with susceptibility to disease, including bleeding and thrombosis.

Idiopathic thombocytopenic purpura (ITP) is defined by the presence of thrombocytopenia in the absence of an identifiable secondary cause.  An autoimmune process has been strongly implicated, yet the molecular mechanisms responsible for ITP are unknown and treatment remains largely empiric.  Our goal is to identify gene(s) involved in the pathogenesis of inherited ITP, which may be implicated in the more common sporadic form of the disease.  We speculate that genes identified in this study could be involved in key pathways involved in humoral immunity and the regulation of tolerance, but platelet-specific phenotypes or novel genes with previously unknown function may also be discovered.

SELECTED PUBLICATIONS

Johnsen JM, Auer PL, Morrison AC, Jiao S, Wei P, Haessler J, Fox K, Carlson CS, Smith N, Boerwinkle E, Kooperberg C, Nickerson D, Rich SS, Green D, Peters U, Cushman M, Reiner AP, on behalf of the NHLBI GO Exome Sequencing Project. Common and rare von Willebrand Factor (VWF) coding variants, VWF levels, and Factor VIII levels in African Americans. In Press, Blood.

Zimring JC, Smith N, Stowell SR, Johnsen JM, Bell LN, Francis R, Hod EA, Hendrickson JE, Roback JD, Spitalnik SL. Strain-specific red blood cell storage, metabolism, and eicosanoid generation in a mouse model. In Press, Transfusion.

Johnsen J. Pathogenesis in immune thrombocytopenia: new insights. Hematology American Society of Hematology Education Program. 2012:306-12. PMID: 23233597.

Auer PL, Johnsen JM, Johnson AD, Logsdon BA, Lange LA, Nalls MA, Franceschini N, Fox K, Lange EM, Rich SS, O'Donnell CJ, Jackson RD, Wallace RB, Chen Z, Graubert TA, Wilson JG, Tang H, Lettre G, Reiner AP, Ganesh SK, Li Y, on behalf of the NHLBI GO Exome Sequencing Project. Imputation of exome sequence variants into population-based samples identifies blood cell trait-associated loci in African Americans: the NHLBI GO Exome Sequencing Project. American Journal of Human Genetics. 91(5):794-808, 2012. PMID: 23103231

Zimring JC, Stowell S, Johnsen JM, and Hendrickson JE. The Effect of Genetic, Epigenetic, and Environmental Factors on Alloimmunization to Transfused Antigens; Current Paradigms and Future Considerations. Transfusion Clinique et Biologique, Jun;19(3):125-31, 2012. PMID:22682308

Zimring JC, Johnsen JM. Keeping the Kell away from immunity. Blood, Jun 7;119(23):5346-8, 2012. PMID:22679338

Staubach F, Kunzel S, Baines AC, Yee A, McGee BM, Backhed F, Baines JF, Johnsen JM. Expression of the glycosyltransferase B4galnt2 influences the intestinal microbiota in mice. The ISME Journal, Jul;6(7):1345-55, 2012. PMID:22278669

Linnenbrink M, Johnsen JM, Montero I, Brzezinksi CR, Harr B, Baines JF. Long-term balancing selection at the blood-group related gene B4galnt2 in the genus Mus (Rodentia; Muridae). Molecular Biology and Evolution, 28(11):2999-3003, 2011. PMID:21652612

Johnsen JM, Teschke M, Pavlidis P, McGee BM, Tautz D, Ginsburg D, and Baines JF. Selection on cis-regulatory variation at B4galnt2 and its influence on von Willebrand Factor in house mice. Molecular Biology and Evolution, 26(3):567-578, 2009. PMID:19088380

Johnsen J, Lpez JA. VWF secretion: whats in a name? Blood, 112(4):926-7, 2008. PMID:18684873

Johnsen J, Levy G, Westrick R, Tucker P, Ginsburg D. The endothelial specific regulatory mutation, Mvwf1, is a common mouse founder allele. Mammalian Genome, 19:32-40, 2008. PMID:18188647