University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Clifford A. Lowell, MD, PhD

Clifford A. Lowell, MD, PhD

Professor, Department of Laboratory Medicine, UCSF

Cancer Center Program Memberships

Hematopoietic Malignancies | Cancer Immunology

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. Zikherman J, Lowell CA. B cell autoimmunity at the extremes. Nat Immunol. 2017 Sep 19; 18(10):1065-1066.
    View on PubMed
  2. Sinha M, Lowell CA. Efficiency and Specificity of Gene Deletion in Lung Epithelial Doxycycline-Inducible Cre Mice. Am J Respir Cell Mol Biol. 2017 Aug; 57(2):248-257.
    View on PubMed
  3. Costa S, Marini O, Bevilacqua D, DeFranco AL, Hou B, Lonardi S, Vermi W, Rodegher P, Panato A, Tagliaro F, Lowell CA, Cassatella MA, Girolomoni G, Scapini P. Role of MyD88 signaling in the imiquimod-induced mouse model of psoriasis: focus on innate myeloid cells. J Leukoc Biol. 2017 Sep; 102(3):791-803.
    View on PubMed
  4. Abram CL, Lowell CA. Shp1 function in myeloid cells. J Leukoc Biol. 2017 Sep; 102(3):657-675.
    View on PubMed
  5. Roubinian NH, Looney MR, Keating S, Kor DJ, Lowell CA, Gajic O, Hubmayr R, Gropper M, Koenigsberg M, Wilson GA, A Matthay M, Toy P, Murphy EL. Differentiating pulmonary transfusion reactions using recipient and transfusion factors. Transfusion. 2017 Jul; 57(7):1684-1690.
    View on PubMed
  6. Chen J, Zhong MC, Guo H, Davidson D, Mishel S, Lu Y, Rhee I, Pérez-Quintero LA, Zhang S, Cruz-Munoz ME, Wu N, Vinh DC, Sinha M, Calderon V, Lowell CA, Danska JS, Veillette A. SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1 integrin. Nature. 2017 04 27; 544(7651):493-497.
    View on PubMed
  7. Poh AR, Love CG, Masson F, Preaudet A, Tsui C, Whitehead L, Monard S, Khakham Y, Burstroem L, Lessene G, Sieber O, Lowell C, Putoczki TL, O'Donoghue RJJ, Ernst M. Inhibition of Hematopoietic Cell Kinase Activity Suppresses Myeloid Cell-Mediated Colon Cancer Progression. Cancer Cell. 2017 Apr 10; 31(4):563-575.e5.
    View on PubMed
  8. Boras M, Volmering S, Bokemeyer A, Rossaint J, Block H, Bardel B, Van Marck V, Heitplatz B, Kliche S, Reinhold A, Lowell C, Zarbock A. Skap2 is required for ß2 integrin-mediated neutrophil recruitment and functions. J Exp Med. 2017 Mar 06; 214(3):851-874.
    View on PubMed
  9. Lee LM, Ji M, Sinha M, Dong MB, Ren X, Wang Y, Lowell CA, Ghosh S, Locksley RM, DeFranco AL. Determinants of Divergent Adaptive Immune Responses after Airway Sensitization with Ligands of Toll-Like Receptor 5 or Toll-Like Receptor 9. PLoS One. 2016; 11(12):e0167693.
    View on PubMed
  10. Sinha M, Lowell CA. Isolation of Highly Pure Primary Mouse Alveolar Epithelial Type II Cells by Flow Cytometric Cell Sorting. Bio Protoc. 2016 Nov 20; 6(22).
    View on PubMed
  11. 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
  12. Proekt I, Miller CN, Jeanne M, Fasano KJ, Moon JJ, Lowell CA, Gould DB, Anderson MS, DeFranco AL. LYN- and AIRE-mediated tolerance checkpoint defects synergize to trigger organ-specific autoimmunity. J Clin Invest. 2016 Oct 03; 126(10):3758-3771.
    View on PubMed
  13. Hang L, Blum AM, Kumar S, Urban JF, Mitreva M, Geary TG, Jardim A, Stevenson MM, Lowell CA, Weinstock JV. Downregulation of the Syk Signaling Pathway in Intestinal Dendritic Cells Is Sufficient To Induce Dendritic Cells That Inhibit Colitis. J Immunol. 2016 Oct 01; 197(7):2948-57.
    View on PubMed
  14. Wang H, Li M, Hung CY, Sinha M, Lee LM, Wiesner DL, LeBert V, Lerksuthirat T, Galles K, Suresh M, DeFranco AL, Lowell CA, Klein BS, Wüthrich M. MyD88 Shapes Vaccine Immunity by Extrinsically Regulating Survival of CD4+ T Cells during the Contraction Phase. PLoS Pathog. 2016 Aug; 12(8):e1005787.
    View on PubMed
  15. 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
  16. Kerr SC, Fischer GJ, Sinha M, McCabe O, Palmer JM, Choera T, Lim FY, 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
  17. Németh T, Mócsai A, Lowell CA. Neutrophils in animal models of autoimmune disease. Semin Immunol. 2016 Apr; 28(2):174-86.
    View on PubMed
  18. 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 06 02; 534(7605):138.
    View on PubMed
  19. 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
  20. 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.
    View on PubMed

Go to UCSF Profiles, powered by CTSI