Clifford A. Lowell, MD, PhD

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Clifford A. Lowell, MD, PhD

Professor, Department of Laboratory Medicine, UCSF

Clifford.Lowell@ucsf.edu

Phone: (415) 476-2963 (voice)
Box 0100, UCSF
San Francisco, CA 94143-0100

UCSF Profiles

Research Summary

My laboratory studies tyrosine kinase based signal transduction in innate immune cells. Our general approach involves examination of innate immune function in knockout mice lacking various members of the Src-family or Syk family of tyrosine kinases. Many of these studies also involve use of mice lacking these kinases in specific hematopoietic lineages, such as neutrophils, macrophages or DCs, generated through Cre/Lox technology. We have also used this approach to study other tyrosine kinases (Pyk2/Fak) and intracellular signaling molecules (WASp, STIM1) in innate immune cells. Our major findings have illuminated the function of Src-family and Syk kinases in leukocyte integrin signaling—loss of these kinases results in significant defects in inflammatory and host defense functions mediated by integrins. We have found that leukocyte integrin signaling utilizes the same intracellular pathways initiated by classical immunoreceptors (e.g., FcγRs) by co-opting ITAM-containing adapter proteins. We have also demonstrated the important ways these kinases regulate innate immune cells in the setting of autoimmune and inflammatory diseases, using the Lyn kinase-deficient model. Ongoing studies also involve examination of tyrosine phosphatases (mainly SHP-1) in the counter regulation tyrosine kinases, especially in the setting of hematopoietic malignancy, as well as studies of calcium signaling proteins, using mice lacking these genes specifically in myeloid lineage cells.

Education

Stanford University, B.S., 1979, Biology
The Johns Hopkins University School of Medicine, M.D., 1986, Medicine
The Johns Hopkins University School of Medicine, Ph.D., 1986, Biochemistry/Molecular Biology


Professional Experience

  • 1986 - 1989
    Osler Medical House Officer (Internship and Residency), Johns Hopkins Hospital. Residency Research Project, Department of Medicine, Laboratory of Dr. Douglas Fearon
  • 1989 - 1995
    Post-Doctoral Research Fellow, Department of Microbiology and Immunology University of California, San Francisco (UCSF). Laboratory of Dr. Harold Varmus.
  • 1990 - 1992
    Clinical Oncology Fellow, Dept. of Medicine, UCSF
  • 1995 - 2001
    Assistant Professor, Dept. Laboratory Medicine, UCSF Director Clinical Immunology Laboratory.
  • 2001 - 2005
    Associate Professor, Dept. Laboratory Medicine, UCSF Director Clinical Immunology Laboratory.
  • 2005 - 2006
    Professor, Dept. of Laboratory Medicine, UCSF Director Clinical Immunology Laboratory.
  • 11/2006 -
    Professor and Chairman, Dept. of Laboratory Medicine, UCSF

Honors & Awards

  • 1979
    Phi Beta Kappa, Stanford University
  • 1979-86
    Medical Scientist Training Program Scholarship, The Johns Hopkins University School of Medicine
  • 1986
    Alpha Omega Alpha, The Johns Hopkins University School of Medicine
  • 1990
    Diplomat of American Board of Internal Medicine
  • 1992
    Awardee Howard Hughes Physician Scientist Training Fellowship
  • 1997
    Awardee American Society of Hematology Junior Faculty Scholar Award
  • 2000
    Awardee Stewart Family Trust Scholar Award
  • 2000
    Awardee Leukemia Research Foundation New Investigator Award
  • 2001
    Awardee Leukemia/Lymphoma Society Scholar Award
  • 2003
    UCSF Immunology Program Annual Student-selected Faculty Speaker
  • 2003
    Appointed Associate Director, UCSF M.D.-Ph.D. (MSTP) Program
  • 2005
    Federation of American Societies for Experimental Biology (FASEB) - elected organizer 2007 meeting

Selected Publications

  1. Iborra S, Martínez-López M, Cueto FJ, Conde-Garrosa R, Del Fresno C, Izquierdo HM, Abram CL, Mori D, Campos-Martín Y, Reguera RM, Kemp B, Yamasaki S, Robinson MJ, Soto M, Lowell CA, Sancho D. Leishmania Uses Mincle to Target an Inhibitory ITAM Signaling Pathway in Dendritic Cells that Dampens Adaptive Immunity to Infection. Immunity. 2016 Oct 18; 45(4):788-801.
    View on PubMed
  2. Sinha M, Lowell CA. Immune Defense Protein Expression in Highly Purified Mouse Lung Epithelial Cells. Am J Respir Cell Mol Biol. 2016 Jun; 54(6):802-13.
    View on PubMed
  3. Kerr SC, Fischer GJ, Sinha M, McCabe O, Palmer JM, Choera T, Yun Lim F, Wimmerova M, Carrington SD, Yuan S, Lowell CA, Oscarson S, Keller NP, Fahy JV. FleA Expression in Aspergillus fumigatus Is Recognized by Fucosylated Structures on Mucins and Macrophages to Prevent Lung Infection. PLoS Pathog. 2016 Apr; 12(4):e1005555.
    View on PubMed
  4. Németh T, Mócsai A, Lowell CA. Neutrophils in animal models of autoimmune disease. Semin Immunol. 2016 Apr; 28(2):174-86.
    View on PubMed
  5. Chen Z, Shojaee S, Buchner M, Geng H, Lee JW, Klemm L, Titz B, Graeber TG, Park E, Tan YX, Satterthwaite A, Paietta E, Hunger SP, Willman CL, Melnick A, Loh ML, Jung JU, Coligan JE, Bolland S, Mak TW, Limnander A, Jumaa H, Reth M, Weiss A, Lowell CA, Müschen M. Corrigendum: Signalling thresholds and negative B-cell selection in acute lymphoblastic leukaemia. Nature. 2016 Jun 2; 534(7605):138.
    View on PubMed
  6. Rosales C, Demaurex N, Lowell CA, Uribe-Querol E. Neutrophils: Their Role in Innate and Adaptive Immunity. J Immunol Res. 2016; 2016:1469780.
    View on PubMed
  7. Volmering S, Block H, Boras M, Lowell CA, Zarbock A. The Neutrophil Btk Signalosome Regulates Integrin Activation during Sterile Inflammation. Immunity. 2016 Jan 19; 44(1):73-87.
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  8. Freedman TS, Tan YX, Skrzypczynska KM, Manz BN, Sjaastad FV, Goodridge HS, Lowell CA, Weiss A. LynA regulates an inflammation-sensitive signaling checkpoint in macrophages. Elife. 2015; 4.
    View on PubMed
  9. Yi T, Li J, Chen H, Wu J, An J, Xu Y, Hu Y, Lowell CA, Cyster JG. Splenic Dendritic Cells Survey Red Blood Cells for Missing Self-CD47 to Trigger Adaptive Immune Responses. Immunity. 2015 Oct 20; 43(4):764-75.
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  10. Prakash A, Sundar SV, Zhu YG, Tran A, Lee JW, Lowell C, Hellman J. Lung Ischemia-Reperfusion is a Sterile Inflammatory Process Influenced by Commensal Microbiota in Mice. Shock. 2015 Sep; 44(3):272-9.
    View on PubMed
  11. Stadtmann A, Block H, Volmering S, Abram C, Sohlbach C, Boras M, Lowell CA, Zarbock A. Cross-Talk between Shp1 and PIPKI? Controls Leukocyte Recruitment. J Immunol. 2015 Aug 1; 195(3):1152-61.
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  12. Mócsai A, Walzog B, Lowell CA. Intracellular signalling during neutrophil recruitment. Cardiovasc Res. 2015 Aug 1; 107(3):373-85.
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  13. Chen Z, Shojaee S, Buchner M, Geng H, Lee JW, Klemm L, Titz B, Graeber TG, Park E, Tan YX, Satterthwaite A, Paietta E, Hunger SP, Willman CL, Melnick A, Loh ML, Jung JU, Coligan JE, Bolland S, Mak TW, Limnander A, Jumaa H, Reth M, Weiss A, Lowell CA, Müschen M. Signalling thresholds and negative B-cell selection in acute lymphoblastic leukaemia. Nature. 2015 May 21; 521(7552):357-61.
    View on PubMed
  14. Clemens RA, Lowell CA. Store-operated calcium signaling in neutrophils. J Leukoc Biol. 2015 Oct; 98(4):497-502.
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  15. Roubinian NH, Looney MR, Kor DJ, Lowell CA, Gajic O, Hubmayr RD, Gropper MA, Koenigsberg M, Wilson GA, Matthay MA, Toy P, Murphy EL. Cytokines and clinical predictors in distinguishing pulmonary transfusion reactions. Transfusion. 2015 Aug; 55(8):1838-46.
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  16. Toy P, Bacchetti P, Grimes B, Gajic O, Murphy EL, Winters JL, Gropper MA, Hubmayr RD, Matthay MA, Wilson G, Koenigsberg M, Lee DC, Hirschler NV, Lowell CA, Schuller RM, Gandhi MJ, Norris PJ, Mair DC, Sanchez Rosen R, Looney MR. Recipient clinical risk factors predominate in possible transfusion-related acute lung injury. Transfusion. 2015 May; 55(5):947-52.
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  17. Kovács M, Németh T, Jakus Z, Sitaru C, Simon E, Futosi K, Botz B, Helyes Z, Lowell CA, Mócsai A. The Src family kinases Hck, Fgr, and Lyn are critical for the generation of the in vivo inflammatory environment without a direct role in leukocyte recruitment. J Exp Med. 2014 Sep 22; 211(10):1993-2011.
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  18. Looney MR, Roubinian N, Gajic O, Gropper MA, Hubmayr RD, Lowell CA, Bacchetti P, Wilson G, Koenigsberg M, Lee DC, Wu P, Grimes B, Norris PJ, Murphy EL, Gandhi MJ, Winters JL, Mair DC, Schuller RM, Hirschler NV, Rosen RS, Matthay MA, Toy P. Prospective study on the clinical course and outcomes in transfusion-related acute lung injury*. Crit Care Med. 2014 Jul; 42(7):1676-87.
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  19. Jaumouillé V, Farkash Y, Jaqaman K, Das R, Lowell CA, Grinstein S. Actin cytoskeleton reorganization by Syk regulates Fc? receptor responsiveness by increasing its lateral mobility and clustering. Dev Cell. 2014 Jun 9; 29(5):534-46.
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  20. Acín-Pérez R, Carrascoso I, Baixauli F, Roche-Molina M, Latorre-Pellicer A, Fernández-Silva P, Mittelbrunn M, Sanchez-Madrid F, Pérez-Martos A, Lowell CA, Manfredi G, Enríquez JA. ROS-triggered phosphorylation of complex II by Fgr kinase regulates cellular adaptation to fuel use. Cell Metab. 2014 Jun 3; 19(6):1020-33.
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