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Scientist Profile

Tim Behrens

Senior Director: Human Genetics
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"Our group is dreaming big, and we hope to drive science forward that will ultimately change the way physicians do differential diagnosis and make treatment decisions."
 

I moved to Genentech in 2006 following 20 years in academia, where my laboratory focused on three major themes: 1) the development of B lymphocytes; 2) the primary genetics of human autoimmune diseases, especially systemic lupus erythematosus; and 3) the identification of biomarkers for lupus and rheumatoid arthritis. Over the last few years, I have been particularly intrigued by the problem of applying cutting-edge genetic and proteomic technologies into the clinic to answer important questions like 'How active is the disease in this patient?', and 'How likely is this patient to respond to a particular drug?' I came to Genentech to build a group that can begin to answer these types of questions.

Genentech's B-cell depletion therapy for rheumatoid arthritis and perhaps other autoimmune diseases, and anti-IgE therapy for allergic asthma are two very important breakthrough treatments for patients with immunologic diseases. Both also provide unique opportunities to identify responder and non-responder subsets of patients, using samples collected from clinical trials. Since the rate-limiting step for most biomarker work is the quality and depth of the clinical data and samples, we are in a unique position at Genentech to make significant progress in this area.

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My Focus

The group we are building is taking a disease-focused approach to the identification of biomarkers that identify subsets of patients within a given disease, markers for disease activity, and biomarkers for responders/nonresponders.

Genentech has an incredible depth of talent across all the groups we interact with, which include bench scientists, clinical scientists, physicians, pharmacologists, and a variety of individuals in the clinical operations, regulatory, business development, and commercial groups. Although the work to identify biomarkers in diseases affecting the immune system takes time, we are hopeful that these efforts will translate eventually into better medical care of patients.

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Publications & Recognition
  • Functional outcome of B cell activation by chromatin immune complex engagement of the B cell receptor and TLR9.
  • J Immunol 2007 Dec 1; 179(11): 7397-405.
  • Busconi L, Bauer JW, Tumang JR, Laws A, Perkins-Mesires K, Tabor AS, Lau C, Corley RB, Rothstein TL, Lund FE, Behrens TW, Marshak-Rothstein A.
  • View Abstract on PubMed
  • AID-deficient Bcl-xL transgenic mice develop delayed atypical plasma cell tumors with unusual Ig/Myc chromosomal rearrangements.
  • J Exp Med 2007 Nov 26; 204: 2989-3001.
  • Kovalchuk AL, duBois W, Mushinski E, McNeil NE, Hirt C, Qi CF, Li Z, Janz S, Honjo T, Muramatsu M, Ried T, Behrens T, Potter M.
  • View Abstract on PubMed
  • STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus.
  • N Engl J Med 2007 Sep 6; 357(10): 977-86.
  • Remmers EF, Plenge RM, Lee AT, Graham RR, Hom G, Behrens TW, de Bakker PI, Le JM, Lee HS, Batliwalla F, Li W, Masters SL, Booty MG, Carulli JP, Padyukov L, Alfredsson L, Klareskog L, Chen WV, Amos CI, Criswell LA, Seldin MF, Kastner DL, Gregersen PK.
  • View Abstract on PubMed
 
View All Publications & Recognition
 
  • University of Minnesota Medical School
  • Adjunct Professor of Medicine
  • 2006
  • Genentech, ITGR Exploratory Clinical Development
  • Senior Director
  • 2006
  • University of Minnesota Medical School, Department of Medicine, Division of Rheumatic and Autoimmune Diseases, Center for Immunology
  • John F. Finn Arthritis Foundation Land Grant Chair and Professor of Medicine
  • 2000-2006
  • University of Minnesota Medical School, Autoimmunity Program, Center for Immunology
  • Chief
  • 1999-2006
  • University of Minnesota Medical School
  • Associate Professor of Medicine
  • 1997-2000
  • University of Minnesota Medical Schoo
  • Assistant Professor of Medicine
  • 1992-1997
  • Metabolism Branch, National Cancer Institute, NIH, Bethesda, Maryland
  • Postdoctoral Fellow under the supervision of Dr. Louis M. Staudt
  • 1989-1992
  • Brookfield Memorial Hospital, Brookfield, Wisconsin, Emergency Room Physician 1988-1989
  • Need content
  • 1992-1997
  • Medical College of Wisconsin, Milwaukee, Wisconsin
  • Rheumatology/Immunology Fellow, Combined clinical and research fellowship under the supervision of Drs. Daniel J. McCarty, Laurence Ryan and James S. Goodwin (American College of Rheumatology, Diplomate 1988)
  • 1986-1989
  • Medical College of Wisconsin, Milwaukee, Wisconsin, Internal Medicine
  • Chief Medical Resident
  • 1985-1986
  • Medical College of Wisconsin, Milwaukee, Wisconsin
  • Internal Medicine Intern/Resident (American Board of Internal Medicine, Diplomate 1986)
  • 1982-1985
Publications & Recognition
  • Functional outcome of B cell activation by chromatin immune complex engagement of the B cell receptor and TLR9.
  • J Immunol 2007 Dec 1; 179(11): 7397-405.
  • Busconi L, Bauer JW, Tumang JR, Laws A, Perkins-Mesires K, Tabor AS, Lau C, Corley RB, Rothstein TL, Lund FE, Behrens TW, Marshak-Rothstein A.
  • View Abstract on PubMed
  • AID-deficient Bcl-xL transgenic mice develop delayed atypical plasma cell tumors with unusual Ig/Myc chromosomal rearrangements.
  • J Exp Med 2007 Nov 26; 204: 2989-3001.
  • Kovalchuk AL, duBois W, Mushinski E, McNeil NE, Hirt C, Qi CF, Li Z, Janz S, Honjo T, Muramatsu M, Ried T, Behrens T, Potter M.
  • View Abstract on PubMed
  • STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus.
  • N Engl J Med 2007 Sep 6; 357(10): 977-86.
  • Remmers EF, Plenge RM, Lee AT, Graham RR, Hom G, Behrens TW, de Bakker PI, Le JM, Lee HS, Batliwalla F, Li W, Masters SL, Booty MG, Carulli JP, Padyukov L, Alfredsson L, Klareskog L, Chen WV, Amos CI, Criswell LA, Seldin MF, Kastner DL, Gregersen PK.
  • View Abstract on PubMed
  • Reexamining the role of TACI coding variants in common variable immunodeficiency and selective IgA deficiency.
  • Nat Genet 2007 Apr; 39(4): 429-30.
  • Pan-Hammarström Q, Salzer U, Du L, Björkander J, Cunningham-Rundles C, Nelson DL, Bacchelli C, Gaspar HB, Offer S, Behrens TW, Grimbacher B, Hammarström L.
  • View Abstract on PubMed
  • Role for Msh5 in the regulation of Ig class switch recombination.
  • Proc Natl Acad Sci U S A 2007 Apr 24; 104(17): 7193-8.
  • Sekine H, Ferreira RC, Pan-Hammarström Q, Graham RR, Ziemba B, de Vries SS, Liu J, Hippen K, Koeuth T, Ortmann W, Iwahori A, Elliott MK, Offer S, Skon C, Du L, Novitzke J, Lee AT, Zhao N, Tompkins JD, Altshuler D, Gregersen PK, Cunningham-Rundles C, Harris RS, Her C, Nelson DL, Hammarström L, Gilkeson GS, Behrens TW.
  • View Abstract on PubMed
  • Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus.
  • Proc Natl Acad Sci U S A 2007 Apr 17; 104(16): 6758-63.
  • Graham RR, Kyogoku C, Sigurdsson S, Vlasova IA, Davies LR, Baechler EC, Plenge RM, Koeuth T, Ortmann WA, Hom G, Bauer JW, Gillett C, Burtt N, Cunninghame Graham DS, Onofrio R, Petri M, Gunnarsson I, Svenungsson E, Rönnblom L, Nordmark G, Gregersen PK, Moser K, Gaffney PM, Criswell LA, Vyse TJ, Syvänen AC, Bohjanen PR, Daly MJ, Behrens TW, Altshuler D.
  • View Abstract on PubMed
  • Elevated Serum Levels of Interferon-Regulated Chemokines Are Biomarkers for Active Human Systemic Lupus Erythematosus.
  • PLoS Med 2006 Dec 19; 3(12): e491.
  • Bauer JW, Baechler EC, Petri M, Batliwalla FM, Crawford D, Ortmann WA, Espe KJ, Li W, Patel DD, Gregersen PK, Behrens TW.
  • View Abstract on PubMed
  • Genetics of autoimmune diseases--disorders of immune homeostasis.
  • Nat Rev Genet 2006 Dec; 7(12): 917-28.
  • Gregersen PK, Behrens TW.
  • View Abstract on PubMed
  • Fine-mapping chromosome 20 in 230 systemic lupus erythematosus sib pair and multiplex families: evidence for genetic epistasis with chromosome 16q12.
  • Am J Hum Genet 2006 May; 78(5): 747-58.
  • Gaffney PM, Langefeld CD, Graham RR, Ortmann WA, Williams AH, Rodine PR, Moser KL, Behrens TW.
  • View Abstract on PubMed
  • A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus.
  • Nat Genet 2006 May; 38(5): 550-5.
  • Graham RR, Kozyrev SV, Baechler EC, Reddy MV, Plenge RM, Bauer JW, Ortmann WA, Koeuth T, González Escribano MF; Argentine and Spanish Collaborative Groups, Pons-Estel B, Petri M, Daly M, Gregersen PK, Martín J, Altshuler D, Behrens TW, Alarcón-Riquelme ME.
  • View Abstract on PubMed
  • Gene expression profiling in human autoimmunity.
  • Immunol Rev 2006 Apr; 210: 120-37.
  • Baechler EC, Batliwalla FM, Reed AM, Peterson EJ, Gaffney PM, Moser KL, Gregersen PK, Behrens TW.
  • View Abstract on PubMed
  • Analysis of families in the multiple autoimmune disease genetics consortium (MADGC) collection: the PTPN22 620W allele associates with multiple autoimmune phenotypes.
  • Am J Hum Genet 2005 Apr; 76(4): 561-71.
  • Criswell LA, Pfeiffer KA, Lum RF, Gonzales B, Novitzke J, Kern M, Moser KL, Begovich AB, Carlton VE, Li W, Lee AT, Ortmann W, Behrens TW, Gregersen PK.
  • View Abstract on PubMed
  • Basal immunoglobulin signaling actively maintains developmental stage in immature B cells.
  • PLoS Biol 2005 Mar; 3(3): e82.
  • Tze LE, Schram BR, Lam KP, Hogquist KA, Hippen KL, Liu J, Shinton SA, Otipoby KL, Rodine PR, Vegoe AL, Kraus M, Hardy RR, Schlissel MS, Rajewsky K, Behrens TW.
  • View Abstract on PubMed
  • Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE.
  • Am J Hum Genet 2004 Sep; 75(3): 504-7.
  • Kyogoku C, Langefeld CD, Ortmann WA, Lee A, Selby S, Carlton VE, Chang M, Ramos P, Baechler EC, Batliwalla FM, Novitzke J, Williams AH, Gillett C, Rodine P, Graham RR, Ardlie KG, Gaffney PM, Moser KL, Petri M, Begovich AB, Gregersen PK, Behrens TW.
  • View Abstract on PubMed
  • PI3K and Btk differentially regulate B cell antigen receptor-mediated signal transduction.
  • Nat Immunol 2003 Mar; 4(3): 280-6.
  • Suzuki H, Matsuda S, Terauchi Y, Fujiwara M, Ohteki T, Asano T, Behrens TW, Kouro T, Takatsu K, Kadowaki T, Koyasu S.
  • View Abstract on PubMed
  • Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus.
  • Proc Natl Acad Sci U S A 2003 Mar 4; 100(5): 2610-5.
  • Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, Shark KB, Grande WJ, Hughes KM, Kapur V, Gregersen PK, Behrens TW.
  • View Abstract on PubMed
  • Visualizing human leukocyte antigen class II risk haplotypes in human systemic lupus erythematosus.
  • Am J Hum Genet 2002 Sep; 71(3): 543-53.
  • Graham RR, Ortmann WA, Langefeld CD, Jawaheer D, Selby SA, Rodine PR, Baechler EC, Rohlf KE, Shark KB, Espe KJ, Green LE, Nair RP, Stuart PE, Elder JT, King RA, Moser KL, Gaffney PM, Bugawan TL, Erlich HA, Rich SS, Gregersen PK, Behrens TW.
  • View Abstract on PubMed
  • Delineating the genetic basis of systemic lupus erythematosus.
  • Immunity 2001 Sep; 15(3): 397-408.
  • Wakeland EK, Liu K, Graham RR, Behrens TW.
  • View Abstract on PubMed
  • CD5 maintains tolerance in anergic B cells.
  • J Exp Med 2000 Mar 6; 191(5): 883-90.
  • Hippen KL, Tze LE, Behrens TW.
  • View Abstract on PubMed
  • A genome-wide search for susceptibility genes in human systemic lupus erythematosus sib-pair families.
  • Proc Natl Acad Sci U S A 1998 Dec 8; 95(25): 14875-9.
  • Gaffney PM, Kearns GM, Shark KB, Ortmann WA, Selby SA, Malmgren ML, Rohlf KE, Ockenden TC, Messner RP, King RA, Rich SS, Behrens TW.
  • View Abstract on PubMed
  • Self-reactive B lymphocytes overexpressing Bcl-xL escape negative selection and are tolerized by clonal anergy and receptor editing.
  • Immunity 1998 Jul; 9(1): 35-45.
  • Fang W, Weintraub BC, Dunlap B, Garside P, Pape KA, Jenkins MK, Goodnow CC, Mueller DL, Behrens TW.
  • View Abstract on PubMed
  • Frequent aberrant immunoglobulin gene rearrangements in pro-B cells revealed by a bcl-xL transgene.
  • Immunity 1996 Mar; 4(3): 291-9.
  • Fang W, Mueller DL, Pennell CA, Rivard JJ, Li YS, Hardy RR, Schlissel MS, Behrens TW.
  • View Abstract on PubMed
  • Cloning and molecular characterization of mouse bcl-x in B and T lymphocytes.
  • J Immunol 1994 Nov 15; 153(10): 4388-98.
  • Fang W, Rivard JJ, Mueller DL, Behrens TW.
  • View Abstract on PubMed
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Awards & Honors
  • Arthritis Foundation Top 10 Advances in Rheumatology 2004 (shared, PTPN22 in SLE) Kunkel Society--2006
  • Arthritis Foundation Top 10 Advances in Rheumatology 2003 (IFN signature in SLE)--2003
  • Kirkland Lupus Scholar--2003-2006
  • Faculty of 1000, Autoimmunity--2001
  • Arthritis Foundation 50th Anniversary 'Hero' Postdoctoral Research Award--2001
  • John F. Finn Arthritis Foundation Land Grant Endowed Chair--2000-2006
  • American Society for Clinical Investigation--2000
  • Edmund L. Dubois Memorial Award for Research in SLE, American College of Rheumatology--1998
  • Leukemia & Lymphoma Society Scholar Award--1997-2002
  • Feltl Family Award for Research in Rheumatic Disease--1995-1996
  • NIH NIAMS Clinical Investigator Award--1995
  • American College of Rheumatology/Arthritis Foundation Investigator Award--1994-1997
  • Terri Gotthelf Lupus Foundation Fellowship, awarded, but declined--1989
  • Leukemia Society of America Special Fellowship--1989-1992
  • Frederic C. McDuffie Arthritis Foundation Postdoctoral Fellowship--1989-1992
  • Edward J. Lennon Award for Research Excellence, First Prize--1988
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Tim Behrens, Senior Scientist and Alex Avardo, Receipent of Free Medicine From the Genentech® Access to Care Foundation, on the cover of Genentech's 2006 Annual Report.