i. educational and professional history a. higher ... · 1987 cook college research scholar with...

COLLEGE OF MEDICINE CURRICULUM VITAE

John David Colgan, Ph.D.

June 4th

, 2013

I. EDUCATIONAL AND PROFESSIONAL HISTORY

A. Higher Education

Year Degree Institution

1987 B.S. Cook College, Rutgers University

New Brunswick, NJ

1989 M.A. Columbia University, New York, NY

1991 M.Phil. Columbia University, New York, NY

1994 Ph.D. Columbia University, New York, NY

Graduate and Postdoctoral Fellowships

Year Fellowship Institution

1989-1992 NIH

Predoctoral

Fellowship

Joint Training Program in Biology and

Chemistry

Department of Biological Sciences

Columbia University

1992-1994 Matilda

Woodard

Alumni

Fellowship

Department of Biological Sciences

Columbia University

1995-1998 Aaron

Diamond

Foundation for

AIDS Research

Postdoctoral

Fellowship

Department of Microbiology

Columbia University College of Physicians and

Surgeons

1998-1999 NIH

Postdoctoral

Fellowship


Columbia University College of Physicians and

Surgeons



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B. Professional and Academic Positions

1. Academic

Year Position Institution

1987-1994 Ph.D. Candidate Department of Biological

Sciences, Columbia University,

New York, NY

1994-1999 Postdoctoral Fellow College of Physicians and

Surgeons of Columbia

University, New York, NY

1999-2004 Associate Research

Scientist

College of Physicians and

Surgeons, Columbia

University, New York, NY

2004-2005 Associate University of Iowa,

Department of Internal Medicine,

Iowa City, IA

2005-2012 Assistant Professor University of Iowa,


Iowa City, IA

2012-

present

Associate Professor University of Iowa,


Iowa City, IA

Jan. 2006-

present

Member, Molecular and

Cellular Biology

Graduate Training

Program

University of Iowa,

Iowa City, IA

Sept. 2006-

present

Member, Immunology

Graduate Training

Program

University of Iowa, Carver

College of Medicine

Iowa City, IA

Sept. 2007-

present

Adjunct Faculty University of Iowa, Anatomy and

Cell Biology Department

Iowa City, IA



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2. Administrative

C. Honors and Awards

Year Honor

1987 Cook College Research Scholar with Highest Honors

Rutgers University, New Brunswick, NJ

1993

Peter Sajovic Memorial Award for Outstanding Graduate Study

in Biology, Department of Biological Sciences

Columbia University, New York, NY

2005 Career Development Award. Specialized Program for Research

Excellence (SPORE), Holden Comprehensive Cancer Center,

University of Iowa, Iowa City, IA

2006 National Scientist Development Grant

American Heart Association

D. Professional Memberships

Year Organization

1994-present American Association for the Advancement of Science

1999-present

American Association of Immunologists

1999-present

Federation of American Societies for Experimental Biology

2005-present Holden Comprehensive Cancer Center, University of Iowa

2010-present American Society for Biochemistry and Molecular Biology


4

II. TEACHING

A. Teaching Assignments

Classroom, Seminar, Teaching Laboratory

COMPLETED TEACHING ASSIGMNENTS

Fall 2005

Fall 2006

Facilitator, Small Group Discussions

Principles of Molecular Biology and Cellular Biology

Biosciences Graduate Program

5 class-hours per semester

Fall 2006 Instructor

Topics and Molecular and Cellular Biology

Molecular and Cellular Biology Graduate Program


Fall 2006

Spring 2007

Instructor

Biosciences Seminar



Fall 2007

Fall 2008

Lecturer

Principles of Molecular Biology and Cellular Biology



Spring 2008

Spring 2009

Lecturer

Graduate Immunology II

Immunology Graduate Program


Fall 2008 Instructor

Advanced Topics in Immunology



Fall 2009 Lecturer

Fundamentals of Gene Expression



Spring

Semester

Facilitator, Small Group Case Discussions

M1 Immunology


II. TEACHING (Cont.)

5

2006-2012

Course taken by all 1st year medical students


CURRENT TEACHING ASSIGNMENTS

Spring

Semester

2009-present

Lecturer

M1 Immunology

Course taken by all 1st year medical students

3 to 6 class-hours per semester

Spring

Semester

2010-present

Lecturer

Graduate Immunology



Fall

Semester

2013

Lecturer

Survey of Immunology



B. Graduate student supervision and committees

Ph.D. Candidates Mentored

June 2006

to Aug. 2010

Ping Lu (co-mentored with P. Rothman)


Fall 2005-August 2010 (degree awarded)

June 2007

to Aug. 2011

Isaiah L. Hankel

Anatomy and Cell Biology Department

July 2007-August 2011 (degree awarded)

June 2009

to present

Jacob V. Gorman


Fall 2008-May 2014 (degree awarded)

Dec. 2009

to present

Jennifer Y. Barr


Fall 2008-present

June 2008

to Nov. 2009

Jonathan J. Zuk


Fall 2007-November 2009

Awarded Master’s Degree



6

June 2007

to Aug. 2008

Ming-Yi Chiang


Fall 2006-2008

Ph.D. Candidate Thesis Committees

Spring 2006

to Fall 2009

Anna Peters, (Bishop Lab)

MSTP & Immunology Graduate Program

Fall 2005-December 2009

Spring 2006

to Fall 2009

Erick Brinks (Griffith Lab)



Spring 2007

to Fall 2009

Brian Kreuger (Price Lab)



Fall 2007

to Fall 2009

Nhat-Long Pham (Harty Lab)



Spring 2007

to Spring

2010

William Tabayoyong (Zavazava lab)


Fall 2005-March 2010

Spring 2007

to Spring

2011

Miranda Curtiss (Rothman Lab)


Fall 2005-April 2011

Fall 2007

to Spring

2012

Alexey Soshnev (Geyer lab)


Fall 2006-June 2012

Spring 2007

to Spring

2012

Eric Van Otterloo (Cornell Lab)


Spring 2006-March 2012

Fall 2008

to Fall 2012

Alex Boyden (Waldschmidt Lab)


Fall 2007-August 2012

Fall 2008

to Fall 2012

Kelly Arcipowski (Bishop Lab)

Molecular and Cellular Biology Program

Fall 2007-November 2012



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Fall 2008

to Spring

2013

Ryan Baxley (Geyer Lab)


Fall 2007-May 2013

Spring 2009

to Fall 2013

Nicole Chapman (Houtman Lab)


Fall 2008-Sept 2013

Spring 2010

to Spring

2014

Gabriel Starbeck-Miller (Harty Lab)


Fall 2008-Jan 2014

Fall 2010

to Fall 2013

Daniel McDermott (Varga Lab)


Fall 2008-July 2013

Fall 2011

to present

Khanh Duong (Levasseur Lab)


Fall 2010-June 2014

Fall 2011

to present

Timothy Rosean (Janz Lab)


Fall 2009-present

Fall 2011

to present

Lauren Workman (Habellah Lab)


Fall 2010-present

Fall 2011

to present

Cory Knudson (Varga Lab)


Fall 2009-present

Fall 2011

to Spring

2014

Kayla Weiss (Varga Lab)


Fall 2009-Spring 2014

Fall 2013

to present

Alicia Wallis (Bishop Lab)


Spring 2013-present

Fall 2013

to present

Eric Elliott (Sutterwala Lab)


Spring 2013-present



8

Spring 2014

to present

Jodi Gullicksrud (Xue Lab)


Fall 2012-present

Ph.D. Candidate Qualifying Exam Committees

Spring 2007 Anna Peters

Immunology Program

Spring 2007 Laura Fraczek

Immunology Program

Spring 2007

Jessica Haverkamp

Immunology Program

July 2007 Brian Kreuger


June 2008 Alexey Soshnev


Sept 2008 Eric Van Otterloo


June 2009 Kelly Arcipowski


June 2009 Ryan Baxley


August 2009 Jennifer Barr


Spring 2012 Khanh Duong


Spring 2012 Mahmood Billal


Spring 2012 Richard Davis


Spring 2012 Shaniya Khan




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Undergraduate student supervision

Summer 2005 Abner Almeda, University of Puerto Rico

Department of Microbiology Summer

Undergraduate Research Program

Summer

2005, 2006,

2007

Julie Schweinfurth, Wartburg University

Undergraduate Research

2006-2008 Bryan Leppert, University of Iowa

Undergraduate Work/Study program

Summer 2007 Michael Witthaus, Minnesota State University,

Immunology Undergraduate Research Program

Summer 2008 , Fairfield University


Summer 2009 Travis Kruger, Wartburg University


Summer 2009 Eric Elliott, Wheaton College,

MSTP Undergraduate Research Program

July 2011-

September

2013

Natalie Manhica


Summer 2012 Kristoffer Auza

Spring 2012 Amani Makkouk


Spring 2012 Farrah Steinke


Fall 2012 Michael Hayes


Fall 2012 Marie Kim


Spring 2013 Breanna Scorza




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Summer 2012 Noelle Waldschmidt


Summer 2013 Paige Tedrick


Sept 2013-

present

Jayne Wolfe


C. Other teaching contributions

Institutional Conferences, Grand Rounds, Journal Clubs, Etc

Jan. 2005 Inflammation Program Seminar:

“Regulation of Th2 Responses by the Prolyl

Isomerase Cyclophilin A”

June 2005 Rheumatology Conference: “Regulation of Th2

Responses by the Prolyl Isomerase Cyclophilin A”

Dec. 2005 Rheumatology Journal Club: “Inducing and

Expanding Regulatory T Cell Populations by

Foreign Antigen”

Jan. 2006 Molecular Biology Graduate Program Seminar:

“Regulation of T Cell Signaling Cascades by the

Prolyl Isomerase Cyclophilin A”

May 2006 Immunology Graduate Program Seminar: “Justy, a

novel mouse gene required for B cell development”

June 2006 Neurosurgery Research Conference: “Justy, a novel

mouse gene required for B cell development”

June 2006 Rheumatology Conference: “Justy, a novel mouse

gene required for B cell development”

June 2007 Rheumatology Conference: “Justy, a novel mouse


April 2008 Rheumatology Conference: “Justy, a novel mouse




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April 2008 Internal Medicine Mid-tenure Presentation:

“The Justy Mutation Identifies a Novel Regulator of

B Cell Development”

October 2010 Allergy and Immunology Grand Rounds: “The Justy

mutation identifies the gene Gon4-like as being

required for B lymphopoiesis”

March 2011 Immunology Grand Rounds: “Role of the

developmental regulator Gon4-like in B

lymphopoiesis”

September

2011

Immunology Program: “Understanding how the

protein Gon4-like regulates B cell development”

May 2012 Immunology Grand Rounds: “Role of the


lymphopoiesis”

April 2014 Immunology Grand Rounds: “Tim-3: Activator or

Suppressor of CD8 T Cell Responses?”

Teaching Committees:

Spring 2012 Medical Education Curriculum Renewal

Mechanisms of Health and Disease

Immunology/Infection Subcommitee

Medical Student Counseling:

Fall 2007 -

2012

MSTP Mentoring Committee (with Eric Hoffman

and Jeff Murray)

National Education Related Presentations:

Formal Study to Improve Teaching Abilities:

Current Research Concerning Teaching:

Local and Regional CME Talks (since 1993 only)

June 2005 Rheumatology Conference: “Regulation of Th2

Responses by the Prolyl Isomerase Cyclophilin A”

June 2006 Rheumatology Conference: “Justy, A novel mouse




12

June 2007 Rheumatology Conference: “Justy, A novel mouse


April 2008 Rheumatology Conference: “Justy, A novel mouse


October 2010 Allergy and Immunology Grand Rounds: “The Justy

mutation identifies the gene Gon4-like as being

required for B lymphopoiesis”

March 2011 Immunology Grand Rounds: “Role of the


lymphopoiesis”

May 2012 Immunology Grand Rounds: “Role of the


lymphopoiesis”

April 2014 Immunology Grand Rounds: “Tim-3: Activator or

Suppressor of CD8 T Cell Responses?”


13

III. SCHOLARSHIP

A. Publications or Creative Works

Peer-reviewed

1. Nurse, K., Colgan J., Denman, R., Wilhelm, J. and Ofengand., J. (1987)

Covalent crosslinking of AcVal-tRNA to Tetrahymena thermophila

cytoplasmic ribosomes and two of its 17S mutants. Biochimie 69: 1105-1112.

2. Denman, R., Colgan, J., Nurse, K. and Ofengand, J. (1988) Crosslinking of

the anticodon of P site bound tRNA to C1400 of E. coli 16S RNA does not

require the participation of the 50S subunit. Nucleic Acids Res. 16: 165-178.

3. Fu, X.-Y., Colgan, J., and Manley, J. L. (1988) Multiple cis-acting sequences

are required for efficient splicing of simian virus 40 small-t antigen pre-

mRNA. Mol. Cell. Bio. 8: 3582-3590.

4. Denman, R., Weitzmann, C., Cunningham, P., Negre, D., Nurse, K., Colgan,

J., Pan, Y.C., Miedel, J. and Ofengand, J. (1989) In vitro assembly of 30S and

70S bacterial ribosomes from 16S RNA containing single base substitutions,

insertions and deletions around the decoding site (C1400). Biochemistry 28:

1002-1011.

5. Denman, R., Negre, D., Cunningham, P., Nurse, K., Colgan, J., Weitzmann,

C. and Ofengand, J. (1989) Effect of point mutations in the decoding site

(C1400) region of 16S ribosomal RNA on the ability of ribosomes to carry out

individual steps of protein synthesis. Biochemistry 28: 1012-1019.

6. Ge, H., Noble, J., Colgan, J. and Manley, J. L. (1990) Polyoma virus small

tumor antigen pre-mRNA splicing requires cooperation between two 3' splice

sites. Proc. Natl. Acad. Sci. USA 87: 3338-3342.

7. Zuo, P., Stanojevic, D., Colgan, J., Han, K., Levine, M. and Manley, J.L.

(1991) Activation and repression of transcription by the gap proteins

hunchback and kruppel in cultured Drosophila cells. Genes & Dev. 5: 254-

264.

8. Colgan, J. and Manley, J.L. (1992) TFIID can be rate limiting in vivo for

TATA-containing, but not TATA-lacking, RNA polymerase II promoters.

Genes & Dev. 6: 304-315.

9. Colgan, J., Wampler, S. and Manley, J.L. (1993) Interaction between a

transcriptional activator and the general transcription factor IIB in vivo. Nature

362: 549-553.


14


15

10. Colgan, J. and Manley, J.L. (1995) Cooperation between core promoter

elements influences transcriptional activity in vivo. Proc. Natl. Acad. Sci. USA

92: 1955-1959.

11. Colgan, J., Ashali, H. and Manley, J.L. (1995) A direct interaction between a

glutamine-rich activator and the N terminus of TFIIB can mediate

transcriptional activation in vivo. Mol. Cell. Bio. 15: 2311-2320.

12. Colgan, J., Yuan, H. E. H., Franke, E.K.F. and Luban, J. (1996) Binding of

the HIV-1 gag polyprotein to cyclophilin A is mediated by the central region

of capsid and requires gag dimerization. J. Virol. 70: 4299-4310.

13. Farmer, G., Colgan, J., Nakatani, Y., Manley, J.L. and Prives, C. (1996)

Functional interactions between p53, TBP, and TAFs in vivo. Mol. Cell. Bio.

16: 4295-4304.

14. Farmer, G., Friedlander, P., Colgan, J., Manley, J.L. and Prives, C. (1996)

Transcriptional repression by p53 involves molecular interactions distinct

from those with the TATA box binding protein. Nucleic Acids Res. 21: 4281-

4288.

15. Burniston, M.T., Cimarelli, A., Colgan, J., Curtis S. P., Bertsch, T. and

Luban, J. (1999) HIV-1 gag polyprotein multimerization requires the

nucleocapsid domain and RNA and is promoted by the capsid-dimer interface

and the basic region of matrix. J. Virol. 73: 8527-8540.

16. Colgan J., Asmal, M., and Luban, J. (2000) Isolation, characterization and

targeted disruption of mouse Ppia: Cyclophilin A is not essential for

mammalian cell viability. Genomics 68: 167-178.

17. Asmal, M., Colgan, J., Naef, F., Magnasco, M., and Luban, J. (2003)

Production of ribosome components in effector CD4+ T cells is accelerated by

TCR stimulation and coordinated by ERK-MAPK. Immunity 19: 535-548.

18. Chen, Y., Yan, S.D., Colgan, J., Zhang, H.-P., Schmidt, A.M., Stern, D. and

Herold, K.C. (2004) Blockade of late stages of autoimmune diabetes by

inhibition of the receptor for advanced glycation endproducts (RAGE). J.

Immunol. 173: 1399-1405.

19. Colgan J., Asmal, M., Yu, B., Schneidkraut, J., Lee, Y., Neagu, M.,

Andreotti, A.H., and Luban, J. (2004) Cyclophilin A regulates TCR signal

strength in CD4+ T cells via a proline-directed conformational switch in the

Tec kinase Itk. Immunity 21: 189-201


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20. Colgan, J., Yu, B., Asmal, M., and Luban, J. (2005) Cyclophilin A-deficient

mice are resistant to immunosuppression by cyclosporine. J. Immunol. 174:

6030-6038.

21. Bisikirska, B., Colgan, J., Luban, J., Bluestone, J.A., and Herold, K.C. (2005)

Human T cell receptor signaling with modified anti-CD3 monoclonal antibody

expands CD8+ T cells and induces regulatory CD8

+CD25

+ cells. J. Clin.

Invest. 115: 2904-2913.

22. Lu, P., Hankel, I.L., Marquardt, A., Knisz, J., Chiang, M-Y., Grosse, J.,

Constien, R., Meyer, T., Schroeder, A., Zeitlmann, L., Al-Alem, U., Friedman,

A., Meyerholz, D.K., Waldschmidt, T.J., Rothman, P.B. and Colgan, J.D.

(2010) The Justy Mutation Identifies the Transcriptional Repressor Gon4l as a

Critical Regulator of B Lineage Commitment. J. Exp. Med. 207: 1359-1367.

23. Hostager, B.S., Fox, D.K., Whitten, D., Wilkerson, C.G., Eipper, B.A.,

Francone, V.P., Rothman, P.B. and Colgan, J.D. (2010) HOIL-1L interacting

protein as an NF-kB regulating component of the CD40 signaling complex.

PLoS One 5: e11380.

24. Kashiwada, M., Colgan, J.D. and Rothman, P.B. NFIL3/E4BP4 controls type

2 helper T cell cytokine expression. (2011) EMBO J. 30: 2071-2082.

25. Curtiss, M.L., Hostager, B.S., Stepniak, E., Singh, M., Manhica, N., Knisz, J.,

Traver, G., Rennert, P.D., Colgan, J.D. and Rothman, P.B. (2011) Fyn binds

to and phosphorylates T cell immunoglobulin mucin domain-1 (Tim-1) Mol.

Immunol. 48: 1424-1431.

26. Lu, P., Hankel, I.L., Hostager, B.S., Swartzendruber, J.A., Friedman, A.D.,

Brenton, J.L. Rothman P.B. and Colgan, J.D. (2011) The developmental

regulator Gon4-like associates with protein YY1, co-repressor Sin3a and

histone deacetylase 1 and mediates transcriptional repression. J. Biol. Chem.

286: 18311-18319.

27. Hostager, B.S., Colgan, J.D. and Rothman, P.B. (2011) The E3 ubiquitin

ligase HOIP is essential for CD40 signaling. PLoS One 6: e23061.

28. Curtiss, M.L., Businga, T.R., Singh, M., Meyerholz, D.K., Kline, J.N., Yagita,

H., Colgan, J.D., Rothman, P.B., Cassel, S.L. (2012) Tim-1 regulates Th2

responses in an experimental asthma model. Eur. J. Immunol., 42: 651-661.

29. Yu, S., Jing, X., Colgan, J.D., Zhao, D.M. and Xue H.H. (2012). Targeting

tetramer-forming GABP isoforms impairs self-renewal of hematopoietic and

leukemic stem cells. Cell Stem Cell 11: 207-219.


17

30. Chiba, S., Baghdadi, M., Akiba, H., Yoshiyama, H., Kinoshita, I., Dosaka-

Akita, H., Fujioka, Y., Ohba, Y., Gorman, J.V., Colgan, J.D., Hirashima, M.,

Uede, T., Takaoka, A., Yagita, H. and Jinushi, M. (2012) Tumor-infiltrating

DCs suppress nucleic acid-mediated innate immune responses through

interactions between the receptor TIM-3 and the alarmin HMGB1. Nat.

Immunol. 9: 832-842.

31. Simons, A.L., Lu, P., Gibson-Corley, K.N., Robinson, R.A., Meyerholz, D.K.

and Colgan, J.D. (2013) The Justy mutant mouse strain produces a

spontaneous murine model of salivary gland cancer with myoepithelial and

basal cell differentiation. Lab Invest. 93: 711-719.

32. Gorman, J.V., Starbeck-Miller, G., Pham, N.L., Traver, G.L., Rothman, P.B.,

Harty, J.T. and Colgan, J.D. (2014) Tim-3 directly enhances CD8 T cell

responses to acute Listeria monocytogenes infection. J. Immunol. 192: 3133-

3142.

33. Duong, K.L., Das, S., Yu, S., Barr, J.Y., Jena, S., Kim, E., Zavazava, N.,

Colgan, J.D., Xue, H.H. and Levasseur, D.N. (2014) Identification of

hematopoietic-specific regulatory elements from the CD45 gene and use for

lentiviral tracking of transplanted cells. Exp. Hematol. Epub ahead of print.

34. Gorman, J.V. and Colgan J.D. (2014) Response to comment on “Tim-3

directly enhances CD8 T cell responses to acute Listeria monocytogenes

infection”. J. Immunol. 193: 467-468.

Non-peer reviewed papers

Books:

Chapters:

1. Ofengand, J., Denman, R., Negre, D., Kryzosiak, W., Nurse, K., and Colgan,

J. (1988) Structural and functional relationships at the decoding site of the

Escherichia coli ribosome. In Structure and expression, vol. 1; from proteins

to ribosomes (ed. R. H. Sarma and M. H. Sarma), 209-228.

2. Negre, D., Cunningham, P., Weitzmann, C., Denman, R., Colgan, J., Nurse,

K. and Ofengand, J. (1989) The role of 16S RNA in ribosome function: in

vitro synthesis, assembly and function of 30S ribosomes containing single

base alterations in the 16S RNA. UCLA Symposium on Molecular Biology of

RNA 94: 209-219.

http://www.ncbi.nlm.nih.gov/pubmed/22842346




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3. Lu, P., Hostager, B.S., Rothman, P.B, and Colgan J.D. (2013) Sedimentation

and immunoprecipitation assays for analyzing protein complexes that mediate

transcriptional repression. Methods in Molecular Biology: Gene Regulation

(ed. M. Binou) 977: 365-383.

Electronic publications:

Abstracts:

1. Colgan, J., Yuan, H. E. H., Franke, E.K.F. and Luban, J. (1995) Binding of

the HIV-1 gag polyprotein to cyclophilin A is mediated by the central region

of capsid and requires gag dimerization. Cold Spring Harbor Symposium on

Retroviruses.

2. Colgan, J., Asmal, M., and Luban, J. (2000) Conditional viability,

haplonsufficient growth defects, cyclosporine resistance and T cell

hyperactivity in cyclophilin A-deficient mice. Keystone Symposium on

Immunophilins: Cellular Functions and Immunosuppressive Drug

Targets, Keystone, CO.

3. Colgan, J., Asmal, M., and Luban, J. (2000) Cyclophilin A regulates CD4+

helper T cell responses. American Association of Immunologists Annual

Meeting, Experimental Biology, Seattle, WA. (ORAL PRESENTATION)


helper T cell function in the absence of cyclosporine. Cold Spring Harbor

Symposium on Gene Expression and Signaling in the Immune System.


helper T cell responses that control to IL-4 expression. Keystone Symposium

on Regulation of Immunity and Autoimmunity, Keystone, CO.

6. Colgan J., Asmal, M., Yu, B., Schneidkraut, J., Lee, Y., Andreotti, A.H., and

Luban, J. (2004) Cyclophilin A regulates TCR signal strength in CD4+ T cells

via interaction with the Tec kinase Itk. Keystone Symposium on

Lymphocyte Activation and Signaling, Steamboat Springs, CO.




Tec kinase Itk. American Association of Immunologists Annual Meeting,

San Diego, CA. (ORAL PRESENTATION)


19




Tec kinase Itk. FASEB Summer Research Conference on Lymphocyte

Activation and Signaling, Snowmass, CO.




Tec kinase Itk. Midwest Autumn Immunology Conference, Chicago, IL

10. Colgan J., Grunig, G. and Luban, J. (2006) Role of Cyclophilin A in atopic

immune responses TCR signal strength in CD4+ T cells via a proline-directed

conformational switch in the Tec kinase Itk. Cold Spring Harbor

Symposium on Gene Expression and Signaling in the Immune System.

11. Hankel, I.L., Knisz, J., Lu, P., Rothman, P.B., Waldschmidt, T.J. and Colgan,

J.D. (2007) Regulation of Justy/Gon4l expression during T cell development.

Midwest Autumn Immunology Conference, Chicago, IL

12. Chiang, M.Y., Lu, P., Rothman, P., Waldschmidt, T. and Colgan, J. (2007)

Justy, a novel mouse gene required for early B cell development. Midwest

Autumn Immunology Conference, Chicago, IL

13. Knisz, J., Chiang, M.Y., Waldschmidt, T.J., Waldschmidt, T., Colgan, J. and

Rothman, P. (2007) Justy is required for the regulation of lineage-specific

genes during B cell development. Midwest Autumn Immunology

Conference, Chicago, IL

14. Lu, P., Knisz, J., Chiang, M.Y., Hankel, I., Colgan, J. and Rothman, P. (2007)

Justy is a crucial regulator of murine B cell development. Midwest Autumn

Immunology Conference, Chicago, IL

15. Colgan, J.D., Marquardt, A., Knisz, J., Grosse, J., Chiang, M.Y., Lu, P.,

Hankel, I.L., Constien, R., Meyer, T., Schroeder, A., Zeitlmann, L., Friedman,

A., Schweinfurth, J., Al-Alem, U., Waldschmidt, T.J. and Rothman, P.B.

(2008) The Justy mutation identifies the putative chromatin regulator Gon4l as

being essential for B lymphopoieisis. Keystone Symposium on Lymphocyte

Activation and Signaling, Snowmass, Utah (ORAL PRESENTATION)

16. Colgan, J.D., Marquardt, A., Knisz, J., Grosse, J., Chiang, M.Y., Lu, P.,

Hankel, I.L., Constien, R., Meyer, T., Schroeder, A., Zeitlmann, L., Friedman,

A., Schweinfurth, J., Al-Alem, U., Waldschmidt, T.J. and Rothman, P.B.

(2008) The Justy mutation identifies the putative chromatin regulator Gon4l as

being essential for B lymphopoieisis. Cold Spring Harbor Meeting on Gene


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Expression and Signaling in the Immune System, Cold Spring Harbor,

NY

17. Lu, P., Marquardt, A., Knisz, J., Grosse, J., Chiang, M.Y., Hankel, I.L.,

Constien, R., Meyer, T., Schroeder, A., Zeitlmann, L., Friedman, A.,

Schweinfurth, J., Al-Alem, U., Waldschmidt, T.J. Rothman, P.B. and Colgan,

J.D. (2009) The Justy mutation identifies the putative chromatin regulator

Gon4l as being essential for B lymphopoieisis. Keystone Symposium on B

Cells in Context, Taos, New Mexico (ORAL PRESENTATION)

18. Lu, P., Marquardt, A., Hankel, I.L., Knisz, J., Grosse, J., Chiang, M.Y.,


Schweinfurth, J., Al-Alem, U., Waldschmidt, T.J. Rothman, P.B. and Colgan,

J.D. (2009) The Justy mutation identifies the putative chromatin regulator

Gon4l as being essential for B lymphopoieisis. FASEB Summer Research

Conference: Molecular Mechanisms of Lymphocyte Differentiation,

Carefree, AZ

19. Lu, P., Hankel, I.L., Marquardt, A., Knisz, J., Grosse, J., Chiang, M.Y.,


Schweinfurth, J., Al-Alem, U., Waldschmidt, T.J., Rothman, P.B. and

Colgan, J.D. (2009) The Justy mutation identifies the transcriptional regulator

Gon4l as being essential for B lymphopoiesis. Abcam Conference:

Transcriptional Mechanisms of Early Lymphocyte Development, San

Diego, CA (ORAL PRESENTATION)

20. Lu, P., Knisz, J., Chiang, M.-Y., Barr, J.Y., Hankel, I.L. and Colgan, J.D.

(2011) Defining the role of the developmental regulator Gon4-like in B

lymphopoiesis. FASEB Summer Conference: Molecular Mechanisms of

Immune Cell Development and Function, Snowmass, CO (ORAL

PRESENTATION)


Harty, J.T. and Colgan, J.D. (2011) Regulation of effector T cell responses by

the surface receptor Tim-3. Cold Spring Harbor Meeting: Harnessing

Immunity to Prevent and Treat Disease, Cold Spring Harbor, NY

22. Barr, J.Y. and Colgan, J.D. (2012) Investigating the role of Gon4-like in cell

cycle regulation and B lymphopoiesis. Cold Spring Harbor Meeting: Gene

Expression and Signaling in the Immune System, Cold Spring Harbor,

NY

23. Gorman, J.V., Starbeck-Miller, G., Traver, G.L., Rothman, P.B., Harty, J.T.

and Colgan, J.D. (2012) The surface molecule Tim-3 augments CD8 T cell


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responses to Listeria monocytogenes infection. FASEB Summer

Conference: Biology of the Immune System, Snowmass, CO


Harty, J.T. and Colgan, J.D. (2013) The surface molecule Tim-3 augments

CD8 T cell responses to Listeria monocytogenes infection. LXXVIII Cold

Spring Harbor Symposium on Quantitative Biology: Immunity and

Tolerance, Cold Spring Harbor, NY

25. Barr, J.Y., Chiang, M.Y. and Colgan, J.D. (2013). The Gon4-like protein is

essential for global gene repression and cell cycle progression during B

lymphopoieisis. FASEB Summer Conference: Molecular mechanisms of

immune cell development and function, Snowmass, CO


Harty, J.T. and Colgan, J.D. (2014) Tim-3 Directly Enhances CD8 T Cell

Responses to Acute Listeria monocytogenes Infection. American Association

of Immunologists Annual Meeting, Pittsburgh, PA. (ORAL

PRESENTATION)

Reviews:

1. Colgan, J. and Rothman, P. (2007) Manipulation of signaling to control

allergic inflammation. Curr. Opin. Allergy Clin. Immunol. 7: 51-56.

2. Curtiss, M. and Colgan, J. (2007) The role of the costimulatory molecule

Tim-1 in the immune response. Immunol. Res. 39: 52-61.

3. Hankel, I.L., and Colgan, J.D. (2010) Signaling and allergic inflammation.

Curr. Opin. Allergy Clin. Immunol. 10: 42-47.

4. Gorman, J.V. and Colgan, J.D. (2014) Regulation of T cell responses by the

receptor molecule Tim-3. Immunol. Res. Epub ahead of print.

Other:

1) Colgan, J. and Rothman, P. (2006) All in the family: IL-27 suppression of TH-

17 cells. Nat. Immunol. 7: 899-901.

B. Areas of Research Interest and Current Projects

Overall Research Interest: Lymphocyte Development and Function

Project 1: The role of Gon4-like in B lymphopoiesis

B cells generate antibodies, which are essential for protective immunity. All B cells

originate from hematopoietic stem cells (HSCs); in response to extrinsic cues, HSCs give

rise to primitive B cell progenitors, which undergo a series of developmental transitions


22

that culminate in the generation of mature, antibody-forming B cells. At an early stage in

this process, B cell progenitors undergo dramatic and widespread reprogramming of gene

expression, resulting in suppression of developmental plasticity and commitment to a B-

lineage fate. These characteristics are sustained for the life of the B cell and are necessary

for homeostasis and functional competence.

Establishment and maintenance of a B-lineage identity requires a core set of DNA-

binding proteins that are known to regulate transcription on a genome-wide scale. Yet,

factors that function downstream of these proteins and help orchestrate global gene

regulation remain mostly undiscovered. Identifying these factors would lead to new

avenues for dissecting how gene expression is coordinated with differentiation and how

cell identities are acquired or lost. Moreover, disruption of mechanisms that impart a B

cell fate is tightly associated with neoplasia stemming from early B cell progenitors,

which is a prevalent form of cancer in humans. Thus, identifying proteins that are critical

for imparting a B-lineage identity could yield information that helps classify B cell

neoplasias more precisely and facilitates the design of new therapies for B cell-derived

cancers.

To advance our understanding of mechanisms underlying B cell development and B-

lineage identity specification, my lab has performed pioneering studies of a mutant mouse

strain named Justy (for just T cells). These animals carry a recessive mutation that

profoundly impairs B cell development but does not overtly affect other aspects of mouse

physiology. We established that the causative genetic lesion is a point mutation that

greatly reduces expression of a protein called Gon4-like, which contains homology to

factors that mediate epigenetic regulation of gene transcription. Our published studies

showed that Justy mutant mice can form primitive B cell progenitors but are unable to

generate B lineage-committed cells. Genome-wide expression profiling indicated that

decreased Gon4-like expression does not prevent expression of key B-lineage genes, but

rather disrupts repression of a host of genes associated with a developmental plasticity

and competing hematopoietic fates. Consistent with these findings, our published

biochemical studies demonstrated that Gon4-like interacts with factors know to mediate

transcriptional repression. Based on these data, we hypothesize that Gon4-like is a critical

component of the machinery that suppresses competing or incompatible gene programs

and thus allows cells to acquire a B-lineage identity. To test our hypothesis, we carrying

out studies to a) define molecular mechanisms underlying the block in B cell

development in Justy mice; 2) functionally connect Gon4-like to the core set of B-lineage

DNA-binding proteins; 3) define gene loci that are directly regulated by Gon4-like and

factors that interact with Gon4-like; 4) identify additional functional partners for Gon4-

like. To carry out these studies, we have developed a set of unique tools, including

antibodies for Gon4-like, cell line models for performing genome-wide studies of gene

regulation and novel mouse strains. Key among the latter are newly-established mouse

strain for ablating the Gon4-like gene in a cell-specific or inducible manner.

Project 2: Role of the surface protein Tim-3 in T cell responses

T cells are critical for protection against microbial infection and neoplasia. Conversely, T

cells have major roles in immune-mediated disease. Thus, defining pathways that regulate

T cell function would help to develop approaches for modulating immune system


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function. Activated T cells express an array of surface molecules that regulate the

magnitude and durability of the T response. Due to their accessibility, these molecules are

viewed as rational therapeutic targets. My lab is currently defining the function of a T cell

surface molecule known as Tim-3 (for T cell immunoglobulin and mucin domain-3). This

protein consists of an extracellular domain with poorly understood ligand specificity and

an intracellular cytoplasmic tail that likely activates signaling cascades. Published data

indicate that targeting Tim-3 with antibodies can have dramatic effects on T cell-

mediated responses in vivo. Remarkably, however, the physiologic role of Tim-3 in T cell

biology remains obscure. We and others have found that CD8 T cells express Tim-3 in

response to stimulation, suggesting that this molecule regulates CD8 T cell functionality.

To test this hypothesis, we compared the CD8 T cell responses in wild-type (WT) and

Tim-3-deficient (Tim-3 KO) mice as induced by infection with the intracellular bacterium

Listeria monocytogenes (LM). We found that, relative to those in WT, the magnitudes of

CD8 T cell responses by Tim-3 KO mice were significantly reduced, which correlated

with decreased expression of cytokines and other effector molecules. We also found that

CD8 T cell responses to secondary LM infections were dramatically reduced in Tim-3

KO mice.

A confounding factor in these studies was that several immune cell types express

Tim-3. To determine whether Tim-3 has a direct effect on CD8 T cell function, we

developed and employed a system in which an equal number of LM-specific WT and

Tim-3 KO CD8 T cells were jointly transferred into wild-type recipients. Afterward, the

recipients were infected with LM and responses by WT and Tim-3 KO CD8 T cells were

analyzed. Similar to that seen in Tim-3 KO mice, effector responses and cytokine

production by Tim-3 KO CD8 T cells were significantly decreased relative to WT. In

addition, the ability of Tim-3 KO CD8 T cells to form memory cells was significantly

impaired. Mechanistic studies indicated that the rate of death by Tim-3 KO CD8 T cells

was normal, but that proliferation by these cells was significantly decreased. Together,

our results indicate that Tim-3 functions to augment the accumulation and functionality of

CD8 T cells. Moreover, our findings at least suggest that antibody-mediated targeting of

Tim-3 acts to boost CD8 T cell function, which contrasts with the current dogma that

Tim-3 antibodies disrupt a negative regulatory pathway.

Based on our data, we are pursuing several lines of investigation to further explore the

role of Tim-3 in T cell biology: a) previous studies showed that Tim-3 expression marks

functionally impaired or “exhausted” CD8 T cells, which arise in vivo due to chronic viral

infection or tumor challenge, and that administration of Tim-3 antibodies helps to reverse

CD8 T cell exhaustion. Therefore, we are developing new strains of mice to determine

how the lack of Tim-3 affects CD8 T exhaustion and functionality in these contexts; b)

we are conducting studies to define the impact of Tim-3 on CD4 T cell function. Our data

indicate that Tim-3 expression marks highly differentiated effector CD4 T cells and that

CD4 T cell responses are blunted in Tim-3 KO mice. Therefore, we are determining how

the lack of Tim-3 affects the functionality of CD4 T cells in vivo. c) Little is known about

the biochemical function Tim-3. Therefore, we are pursuing a proteomic approach to

identify molecules that can interact with the cytoplasmic tail of Tim-3.

C. Published Reviews of Scholarship


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D. Grants Received

Federal:

Title: (Include source and PI in parenthesis)

Amount Period % Effort % Salary

P30DK063608 (Acilli, D., Director)

Diabetes and Endocrinology Research

Center, Columbia University Pilot Grant

“Effects of Cyclosporine on Islet Cell

Transplants” (NIH/NIDDK; John Colgan,

PI) Universities Center for AIDS Research

$50,000 annual direct

Jan 2003-Dec 2005

25% 25%

P50CA097274 (Weiner, G., Director) NCI Special Program for Research Excellence (SPORE), Holden Comprehensive Cancer Center Career Development Award

“SOCS Proteins in Human Hematopoietic

Cancers” (NIH/NCI; John Colgan, PI)


Jan 2005-Dec 2005

20% 20%

R01AI067489 “Regulation of Atopic

Immune Responses by the

Prolyl Isomerase Cyclophilin A”

(NIH/NIAID; John Colgan, PI)


March 2006- Feb 2011

70% 70%

R01AA019568 “Chronic Alcohol Abuse

Disrupts CD8+ T Cell Function”

(NIH/NIAAA; Robert Cook, PI)

Role: co-investigator


Sept 2009-Aug 2014

12% 12%

R56AI093737 “Role of the developmental

regulator Gon4-like in B lymphopoiesis”



Aug 2011- Dec 2011

70% 65%

R01AI093737 “Role of the developmental

regulator Gon4-like in B lymphopoiesis”



Dec 2011-Nov 2016

70% 65%

State

Title: (Include source and PI in parenthesis)

Amount Period % Effort % Salary


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College of Medicine

Title: (Include source in parenthesis) Amount Period % Effort % Salary

Defining the biochemical function of

Gon4-like, a protein required for B cell

development in mice. (Medical Research

Initiative Grant, Carver Trust; John Colgan,

PI)

$30,000 direct

March 2011-Feb 2012

10% 0%

Other

Title: (Include source in parenthesis) Amount Period % Effort % Salary

Research Grant “The Native Function of

Cyclophilin A in Helper T Cells”

(Columbia and Rockefeller Universities

Center for AIDS Research; John Colgan,

PI)


2000-2001 50% N/A

0535536N National Scientist Development Grant

Regulation of the Tyrosine kinase Itk by

the Cyclosporine Receptor Cyclophilin A (American Heart Association; John Colgan, PI)


2005-2008 (given up in 2006 due to overlap by NIH R01)

60% 20%

E. Invited Lectures

2010 University of Connecticut Medical Center, Department of Immunology,

Farmington, CT

Conference presentations:

ORAL PRESENTATIONS:

2000 American Association of Immunologists Annual Meeting,

Experimental Biology, Seattle, WA

2001 Keystone Symposium on Regulation of Immunity and Autoimmunity

Keystone, CO

2005 American Association of Immunologists Annual Meeting,

Experimental Biology, San Diego, CA

2008 Keystone Symposium on Lymphocyte Activation and Signaling,

Snowmass, Utah

2009 Keystone Symposium on B Cells in Context, Taos, N.M

2009 Abcam Symposium on Transcriptional Regulation of Lymphocyte

Development, San Diego, CA

2011 FASEB Summer Conference: Molecular mechanisms of immune cell

development and function, Snowmass, CO


26

Visiting professorships:

F. Pending Decisions (grant proposals, book contracts)

IV. SERVICE

Editorial Board:

2010-present Review Editor for Frontiers in B Cell Biology

Adhoc Manuscript Review

2005 Journal of Clinical Investigation (1 article)

2006 Nature Immunology (2 articles)

2007 Nature Immunology (6 articles)

2009 Journal of Immunology (1 article)

2010 Journal of Immunology (1 article)

2010 Journal of Experimental Medicine (1 article)

2010 Nature Immunology (1 article)

2010 European Journal of Immunology (1 article)

2011 PLoS ONE (2 articles)

2011 Journal of Leukocyte Biology (1 article)

2011 Nature Immunology (1 article)

2011 New York Academy of Sciences (review article for Immunology volume)

2012 Frontiers in B Cell Biology (7 articles)

2012 Journal of Immunology (2 articles)

2014 Nature Communications (1 article)

Adhoc Grant Application Review

2009 NIH ARRA grant review

2010 NIH/CSR Special Emphasis Panel ZAI1-RRS-I-M2

2010 French National Research Council, reviewer for “Integrated Mechanisms of

Inflammation” Grant Program

2011 NIH/CSR Special Emphasis Panel ZRG1-IMM-N03

Departmental, collegiate, or university committees:

CCOM Representative for Faculty Senate, April 2013-present

Member, Institutional Animal Care and Use Committee, Aug 2008– July 2014

Co-chair, Institutional Animal Care and Use Committee, June 2012- Aug 2014

Search Committee, Chairman for Department of Orthopedics, Carver College of

Medicine, 2014

Member, Internal Medicine Department Compensation Committee, Research

Track Faculty Representative, 2011-present

Departmental Mentoring Committees for Denise Zingman, Fayyez Sutterwala and


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Suzanne Cassel

Member, Immunology Graduate Program Executive Committee 2009-2012; 2013-

present

Member, Immunology Graduate Program Seminar Committee, 2008-present

Chair, Immunology Graduate Program Seminar Committee 2008-2011

Member, Molecular and Cellular Biology Admissions Committee, 2006-2009

Chair, Molecular and Cellular Biology Admissions Committee, 2007-2009

Member, Immunology Graduate Program Admissions Committee, Fall 2013-

present

Departmental, collegiate, or university service positions:

Reviewer, Carver College Medical Research Initiative Grants (2006, 2007)

Reviewer, Carver Collaborative Pilot Grants (2006, 2007)

Reviewer, M1 and pre-M1 fellowship proposals (2007)

Reviewer, M1 fellowship proposals (2008, 2011)

Reviewer, pre-M1 fellowship proposals (2009)

Poster Judge, Medical Student Research Day (2006-2012)

Poster Judge COM Research Week (2009)

University representative at the Society for the Advancement of Chicano and

Native American Scientists (SACNAS) Annual Conference.

October 2008, Salt Lake City, Utah

October 2009, Dallas, Texas

October 2010, Anaheim, California


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i. educational and professional history a. higher ... · 1987 cook college research scholar with...

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