Location out of bounds
Radial
Radial

Directory

All Investigators
Shawn M. Jobe, M.D., Ph.D.

Shawn Jobe, MD, PhD

Medical Director, Comprehensive Center of Bleeding Disorders (CCBD)
Associate Investigator

Associate Investigator
Blood Research Institute

Associate Professor
Department of Pediatrics and Cell Biology, Neurobiology, and Anatomy

Education and Training

Postdoctoral Training
University of Iowa Carver College of Medicine, Residency and Fellowship, 2007

Doctoral Training
Medical College of Wisconsin, 1999

Contact Us

Shawn Jobe, MD, PhD

Medical Director, Comprehensive Center of Bleeding Disorders (CCBD)
Associate Investigator
414-257-2424 Fax: 414-937-6580

  • Research Interests

    Platelets are required to stop bleeding, but inappropriate platelet adhesion and activation results in thrombosis.  In facilitating these responses, platelets undergo dramatic changes in form and function. Our laboratory studies how molecular and cellular events in the platelet are coordinated to link primary hemostasis (VWF binding and platelet aggregation), secondary hemostasis (coagulation), and wound healing and inflammation.  Laboratory, translational, and clinical research methods are all utilized in pursuit of these questions.

    Current projects

    Platelets and mitochondria

    Some aspects of platelet activation resemble events occurring in cell death, which is closely linked with mitochondrial events. Our lab has demonstrated that mitochondrial permeability transition pore (mPTP) formation regulates the transition of platelets from an early activated and proaggregatory phenotype to a terminal procoagulant phenotype. Ongoing studies are focused on the intracellular regulation of platelet mPTP formation and how platelet mPTP formation initiates changes in platelet form and function. Utilizing cyclophilin D (CypD null) mice and other murine models with impaired procoagulant platelet formation, we are also investigating how platelet mPTP formation regulates hemostasis and thrombosis in vivo. Examples of the laboratory techniques used include flow cytometry to evaluate extracellular and intracellular platelet events (receptor expression, calcium fluxes, mitochondrial depolarization, etc); microfluidic flow chamber analysis to study platelet adhesion and thrombosis; and in vivo models of hemostasis and thrombosis.

    When platelets are strongly stimulated, formation of the mitochondrial permeability transition pore (mPTP) is initiated in a platelet subpopulation. mPTP formation then transitions the platelet from an activated and proaggregatory phenotype to a procoagulant phenotype.

    Phenotypic severity in severe hemophilia

    Untreated patients with severe hemophilia suffer severe arthropathy and disability due to frequent bleeding with their joints. Factor replacement has resulted in greatly improved outcomes. However, even with factor replacement, patients with similarly low factor levels have disparate outcomes. Some patients bleed despite seemingly appropriate factor replacement while others have only minimal bleeding despite requiring minimal factor replacement. In this translational study performed in collaboration with Emory University, we are investigating potential biologic and mechanical determinants of this variability; among these are platelet function and procoagulant platelet formation, variability in gait mechanics and activity, and genetic contributions.

  • Grant Support

    Active Support

    2009 - 2014  
    NIH R01 HL095858
    The platelet mitochondrial permeability transition and thrombosis
    Role: Principal Investigator                      

    2012 - 2017  
    NIH U54 HL122309-01
    Translation Research Center in Thrombotic and Hemostatic Disorders
    Biologic Variation in Hemophilia (Lollar, PI)
    Role: Project D lead; "Novel assays predicting phenotypi heterogeneity in sever hemophilia A"
    Role: Project C co-investigator; Project Aim: Epitope spectrum of anti-FVIII antibodies and its relationship to clinical outcomes (2012-2013)
    Role: Core D Director - Biorepository (2012-2013) 
     

    Previous Support

    2006 - 2011
    American Heart Association Fellow-to-Faculty Transition Award
    Role: Principal Investigator
    Description: This program provides funding for trainees with outstanding potential for careers as physician-scientists in cardiovascular or stroke research.

  • Lab

    Andaleb Kholmukhamedov, MD
    Research Scientist I

    Rae Janecke
    Research Technologist II

    Chad Skaer
    Research Technologist I

  • Publications

    Peer Reviewed Publications

    • Pease LR, Horton RM, Pullen JK, Hunt HD, Yun TJ, Rohren EM, Prescott JL, Jobe SM, Allen KS. Amino acid changes in the peptide binding site have structural consequences at the surface of class I glycoproteins. J Immunol 1993; 150: 3375-81.
    • Molkentin JD, Brogan RS, Jobe SM, Markham, BE. Expression of the a-myosin heavy chain gene in the heart is regulated in part by an E-box dependent mechanism. J Biol Chem 1993; 268:2602-9.
    • Molkentin JD, Jobe SM, Markham BE. a-Myosin heavy chain gene regulation: Delineation and characterization of the cardiac muscle-specific enhancer and muscle-specific promoter. J Mol and Cell Cardiology 1996; 28: 1211-25.
    • Herzig TC*Jobe SM*, Aoki H, Molkentin JD, Cowley, Jr AW, Izumo S, Markham BE. Angiotensin II type 1a receptor gene expression in the heart: AP-1 and GATA-4 participate in the response to pressure overload. Proc Natl Acad Sci USA 1997; 94: 7543-8.  *These authors contributed equally.
    • Hasegawa K, Lee SJ, Jobe SMMarkham BE, Kitsis RN. Cis-acting sequences that mediate induction of b-myosin heavy chain gene expression during left hypertrophy due to aortic constriction. Circulation 1997; 96: 3943-53.
    • Lee Y, Shoi T, Kasahara H, Jobe SM, Wiese RJ, Markham BE, Izumo S. The cardiac tissue-restricted homeobox protein Csx/Nkx2.5 physically associates with the zinc finger protein GATA-4 and cooperatively activates atrial natriuretic factor gene expression. Mol Cell Bio 1998;18: 3120-9.
    • Jobe S, Donohoue P, Di Paola J. 2004. Deep venous thrombosis and Turner syndrome. J Ped Hem Onc 2004; 26(4): 272.
    • Jobe SM, Leo L, Eastvold J, Dickneite G, Ratliff T, Lentz SR, Di Paola J. Role of FcRγ and FXIII in platelet procoagulant activity and coated platelet formation. Blood 2005;106:4146-51.
    • Jobe SM., Wilson KM, Leo L, Molkentin JD, Lentz SR, Di Paola J. Critical role for the mitochondrial permeability transition pore (MPTP) and cyclophilin D in platelet activation and thrombosis. Blood 2008; 111:1257-65.
    • Ide LM, Iwakoshi NN, Gangadaharan B, Jobe S, Moot R, McCarty D, Doering CB, Spencer HT. Functional aspects of factor VIII expression after transplantation of genetically-modified stem cells for hemophilia A. J Gene Med 2010; 12(4):333-44.
    • Sabnis H, Kirpalani A, Horan J, McDowall A, Svensson L, Cooley A, Merck T, Jobe S, Hogg N, Briones M. Leukocyte adhesion deficiency-III in an African-American patient. Pediatric Blood Cancer 2010; 55(1): 180-2.
    • Kahr WH, Hinckley J, Li L, Schwertz H, Christensen H, Rowley JW, Pluthero FG, Urban D, Fabbro S, Nixon B, Gadzinski R, Storck M, Wang K, Ryu GY, Jobe SM, Schutte BC, Moseley J, Loughran NB, Parkinson J, Weyrich AS, Di Paola J. Mutations in NBEAL2, encoding a BEACH protein, cause gray platelet syndrome. Nat Genet. 2011; 43(8): 738-40.
    • WangYC, Jobe SM, DingX, ChooHJ, ArcherD, MiR, JuT-Z, Cummings RD. Platelet functions require correct protein O-glycosylation. Proc Natl Acad Sci, USA 2012; 109(40):16143-8.
    • Choo HJ, Saafir TB, Wagner MB, Jobe SM. Mitochondrial calcium and reactive oxygen species regulate agonist-initiated platelet phosphatidylserine exposure. Arterioscler Thromb Vasc Biol. 2012; 32 (12); 2946-55.
    • Mattheij NJ, Gilio K, van Kruchten R, Jobe SM, Wieschhaus AJ, Chishti AH, Collins P, Heemskerk JW, Cosemans JM. Dual mechanism of integrin αIIbβ3 closure in procoagulant platelets.J Biol Chem. 2013; 288(19):13325-36.
    • Liu F, Clemmons W, Gamez G, Myers D, Lam W, Jobe SM. Mitochondrially-mediated integrin αIIbβ3 inactivation limits thrombus growth. J Biol Chem. 2013; 288(42); 30672-30681.
       

    Review Articles and Chapters

    • Jobe, SM, Di Paola J. Acquired and inherited disorders of platelet number and function. In: Kitchens CS, Alving BM, Kessler CM, eds. Consultative Hemostasis and Thrombosis (2nd ed). Elsevier. 2007.
    • Abshire TC, Jobe SM. An overview of the coagulation system. In: Hillyer CD, Shaz BH, Zimring,JC, and Abshire TC, eds. Transfusion Medicine and Hemostasis (1st ed). 2009
    • Jobe SM. Congenital thrombocytopenia. In: Hillyer CD, Shaz BH, Zimring,JC, and Abshire TC, eds. Transfusion Medicine and Hemostasis (1st ed). 2009.
    • Jobe SM. Bernard-Soulier syndrome and other GPIb-IX-V related receptor defects. In: Hillyer CD, Shaz BH, Zimring,JC, and Abshire TC, eds. Transfusion Medicine and Hemostasis (1st ed). 2009.
    • Jobe SM. Glanzmann’s thrombasthenia. In: Hillyer CD, Shaz BH, Zimring,JC, and Abshire TC, eds. Transfusion Medicine and Hemostasis (1st ed). 2009
    • Jobe SM. Platelet storage granule defects. In: Hillyer CD, Shaz BH, Zimring,JC, and Abshire TC, eds. Transfusion Medicine and Hemostasis (1sted). 2009.
    • Jobe SM. Failure to release and aspirin-like defects. In: Hillyer CD, Shaz BH, Zimring,JC, and Abshire TC, eds. Transfusion Medicine and Hemostasis (1sted). 2009.
    • Jobe, SM, Di Paola J. Congenital and acquired disorders of platelet number and function. In: Kitchens CS, Kessler CM, Konkle BA, eds. Consultative Hemostasis and Thrombosis (3nd ed). Elsevier. 2013.
    • Abshire TC, Jobe SM. An overview of the coagulation system. In:, Shaz BH, Hillyer CD, Roshal M, and Abrams CS, eds. Transfusion Medicine and Hemostasis: Clinical and Laboratory Aspects. (2nd ed). Elsevier. 2013.
    • Jobe SM. Bernard-Soulier syndrome and other GPIb-IX-V related receptor defects. In:, Shaz BH, Hillyer CD, Roshal M, and Abrams CS, eds. Transfusion Medicine and Hemostasis: Clinical and Laboratory Aspects. (2nded). Elsevier. 2013.
    • Jobe SM. Glanzmann thrombasthenia In:, Shaz BH, Hillyer CD, Roshal M, and Abrams CS, eds. Transfusion Medicine and Hemostasis: Clinical and Laboratory Aspects. (2nd ed). Elsevier. 2013.
    • Jobe SM. Platelet storage granule defects. In:, Shaz BH, Hillyer CD, Roshal M, and Abrams CS, eds. Transfusion Medicine and Hemostasis: Clinical and Laboratory Aspects. (2nd ed). Elsevier. 2013.
    • Jobe SM. Failure to release and aspirin-like defects. In:, Shaz BH, Hillyer CD, Roshal M, and Abrams CS, eds. Transfusion Medicine and Hemostasis: Clinical and Laboratory Aspects. (2nd ed). Elsevier. 2013.
       

    Abstracts - Peer Reviewed

    • Jobe SM, Wolf JA, Shi XZ, Molkentin JD, Markham BE. 1994. Identification and characterization of two cDNA clones encoding cardiac basic helix-loop-helix proteins. Circulation 90:I-634. Oral presentation.
    • Jobe SM, Lin YG, Wilcox K, Markham BE. 1995. Regulation of cardiac gene expression by GATA-4: A zinc finger is required for interactions with the transcription initiation complex. Circulation 92: I-759. Oral presentation.
    • Jobe SM, Wiese RJ, Markham BE. 1996. GATA-4 and thyroid hormone receptor interact synergistically on a-myosin heavy chain regulatory sites. Circulation 94:I-525. Oral presentation.
    • Koji H, Lee SJ, Jobe SM, Markham BE, Kitsis RN. 1997. A GATA element mediates aortic constriction-responsive transcription of the b-myosin heavy chain gene during cardiac hypertrophy in adult rats. Circulation 96: I-2496. Oral presentation.
    • Jobe SM. COAT platelets: The role of FXIIIa and serotonin in the activated platelet. Pediatric Research Day, University of Iowa. April, 2004.
    • Jobe, SM, Leo L, Dickneite G, Lentz SR, Di Paola J. Murine platelets retain high amounts of alpha granule proteins on their surface upon stimulation with multiple agonists. Blood 104 (11): 61b.
    • Jobe SM, Leo L,Dickneite G, Lentz SR, Di Paola J. Role of FcRγ and FXIII in coated platelet formation and platelet procoagulant activity in mice. International Society on Thrombosis and Hemostasis Meeting, Sydney, AU. 2005. Poster presentation.
    • Jobe SM, Lentz SR, Di Paola J. Oxidant signaling as a mediator of platelet procoagulant activity and coated platelet formation. International Society on Thrombosis and Hemostasis Meeting, Sydney, AU. 2005. Oral communication.
    • Jobe SM, Lentz SR, Di Paola J. Mitochondrial reactive oxygen species (ROS) are involved in coated platelet formation and platelet procoagulant activity. American Society of Hematology,  Atlanta. 2005. Poster presentation.
    • Jobe SM, Wilson KM, Molkentin JD, Lentz SR Di Paola J. Critical role for cyclophilin D and the mitochondrial permeability transition pore (MPTP) in platelet activation. American Society of Hematology, Orlando. 2006. Oral communication (Special Session on Thrombosis and Hemostasis) and poster presentation.
    • Jobe SM, Wilson KM, Leo L, Raimondi A, Molkentin JD, Lentz SR, Di Paola J. Critical role for cyclophilin D (CypD) and the mitochondrial permeability transition pore (MPTP) in the regulation of platelet activation and thrombosis. International Society on Thrombosis and Haemostasis Meeting, Geneva, SW. 2007. Oral communication.
    • Jobe SM, Clemmons W. Accelerated thrombosis in a mouse model with impaired mitochondrial signaling. International Society on Thrombosis and Haemostasis Meeting, Boston MA. 2009. Oral communication.
    • Choo H-J, Saafir T, Wagner M, Jobe S. Changes in mitochondrial permeability initiate platelet phosphatidylserine exposure in response to elevated cytoplasmic calcium levels. American Society of Hematology, Orlando, 2010. Poster presentation.
    • Wang Y, Jobe S, Ding X, Archer DR, Mi R, Ju T, Cummings R. Cosmc is essential for O-glycosylation of platelet glycoproteins and platelet function. American Society of Hematology, Orlando, 2010. Oral communication.
    • Choo H-J, Saafir T, Wagner M, Jobe S. Calcium acts upstream of mitochondrial events to regulate platelet PS exposure. International Society on Thrombosis and Haemostasis Meeting, Kyoto JP, 2011. Poster presentation.
    • Li F, Gamez G, Clemmons W, Jobe SM. Mitochondrially-mediated integrin alphaIIb beta3 inactivation limits platelet recruitment and thrombus growth. International Society on Thrombosis and Haemostasis Meeting, Kyoto JP, 2011. Oral communication.
    • Mattheij NJA, Gilio K, von Kruchten R, Feijge MAH, Bevers EM, Jobe SM, Cosemans JMEM, Heemskerk JWM. Regulation of integrin closure in procoagulant platelets. . International Society on Thrombosis and Haemostasis Meeting, Kyoto JP, 2011. Poster presentation.
    • Liu F, Gamez G, Myers DR, Lam W, Jobe SM. Mitochondrially-mediated integrin alphaIIb beta3 inactivation limits platelet recruitment and thrombus growth. American Society of Hematology, San Diego, 2011. Poster presentation.
    • Choo H-J, Jobe SM. Regulation of platelet procoagulant activity by mitochondrial calcium influx. American Society of Hematology, San Diego, 2011. Poster presentation.
    • Liu F, Jobe SM.  Shear stress initiates cyclophilin D-dependent phosphatidylserine exposure and integrin αIIbβ3 cleavage in platelets. American Society of Hematology, Atlanta, 2012.  Poster presentation.
    • Jobe S, Schenk M , Zhou C-J , Choo H-J , Gibbins J , Lamb T. Does platelet activation mediate pathogenesis of malaria infection?, International Society on Thrombosis and Haemostasis Meeting, Amsterdam, 2013. Oral presentation
    • Choo H-J, Jobe S. Inner mitochondrial membrane disruption is closely associated with both Bax/Bak and cyclophilin D-mediated platelet phosphatidylserine exposure. International Society on Thrombosis and Haemostasis Meeting, Amsterdam, 2013. ePoster presentation
    • Liu F, Jobe S. Mitochondrial permeability transition pore dependent intracellular pH elevation is associated with enhanced calpain activity and integrin aIIbß3 inactivation. International Society on Thrombosis and Haemostasis Meeting, Amsterdam, 2013. ePoster presentation
    • Choo H-J, Jobe S. Aggregation of PS exposing platelets and activated (non-PS exposing) platelets. International Society on Thrombosis and Haemostasis Meeting, Amsterdam, 2013. ePoster presentation.
    • Zhou C-J ,Gangadharan B, Jobe S. A novel non-antibody mediated model of thrombocytopenia allows efficient adoptive transfer of platelets and assessment of platelet function. International Society on Thrombosis and Haemostasis Meeting, Amsterdam, 2013. ePoster presentation.
    • Dunn, A, Taylor L, Jobe S. FVIII genotype and correlation with the hemophilia severity score. International Society on Thrombosis and Haemostasis Meeting, Amsterdam, 2013. ePoster presentation.
ic-arrow-right
x

This website uses cookies to ensure you get the best experience on our website. Learn more