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Achsah D. Keegan, PhD

Academic Title:

Professor

Primary Appointment:

Microbiology and Immunology

Administrative Title:

Associate Director, Medical Scientist Training Program

Location:

Bio Park

Phone (Primary):

(410) 706-8174

Fax:

(410) 706-8234

Education and Training

B.S. Zoology, Duke University, 1983

Ph.D. Molecular Biology and Genetics (Immunology), Johns Hopkins University School of Medicine, 1989

Post-doctoral fellow, Laboratory of Immunology, NIAID, NIH, 1989-1994

Biosketch

Achsah Dorsey Keegan, Ph.D. is a tenured Professor in the Department of Microbiology and Immunology, a member of the Center for Vascular and Inflammatory Diseases (CVID), and is Associate Director of the Medical Scientist Training Program at the University of Maryland School of Medicine. 

Dr. Keegan completed a Bachelor of Science Degree in Zoology with honors (magna cum laude) from Duke University in 1983 and was elected to Phi Beta Kappa. She received her Ph.D. in Immunology from the Department of Molecular Biology and Genetics at the Johns Hopkins University School of Medicine in 1989.  She then joined the National Institute of Allergy and Infectious Disease at the NIH as a National Research Council Associate for her post-doctoral training. In 1994, she joined the Immunology Department at the Holland Laboratory of the American Red Cross as a Staff Scientist (Assistant Professor equivalent), and rose through the ranks to Senior Scientist (Professor equivalent) and served as Deputy Chief of the Department of Immunology. During this tenure, Dr. Keegan was also on the faculty of the George Washington University Medical Center in Washington, where she served as the Director of the Graduate Program in Immunology from 2001-2004. 

She moved to the University of Maryland School of Medicine in 2004 to join the Center for Vascular and Inflammatory Diseases and the Program in Oncology of the University of Maryland Marlene and Stewart Greenebaum Cancer Center. Dr. Keegan is well-recognized for her work studying the mechanism by which two cytokines, Interleukin-4 (IL-4) and Interleukin-13 (IL-13), control Type II inflammatory responses that occur in allergic asthma. Her group studies the basic mechanisms of IL-4 and IL-13 signaling through their receptor complexes, and the regulation of innate immune cell development and function in the context of allergic asthma.  Furthermore, she examines the contribution of these cytokines and their signaling pathways to tumor cell survival.  Recent work has identified the contribution of IL-4-activated macrophage differentiation to the severity of allergic asthma.  Dr. Keegan’s research program has been continuously funded since 1996. 

Dr. Keegan has been an active educator and mentor, having trained 8 PhD students, 7 post-doctoral fellows, and 4 junior faculty members. Furthermore, she has served on more than 30 PhD thesis committees. Dr. Keegan is currently an Associate Editor of Cellular Immunology and the Journal of Interferon and Cytokine Research and is on the Editorial Board of Cytokine. She is a member of the American Association of Immunologists, American Society for Biochemistry and Molecular Biology, International Cytokine and Interferon Society, and the Society for Leukocyte Biology. Dr. Keegan has served as a standing member of the Cellular and Molecular Immunology-A study section (1999-2003) and the Cellular and Immunology-B study section (2010-2014) in the Center for Scientific Review. 


 

Research/Clinical Keywords

cytokines, signal transduction, IL-4, IL-13, receptors, STAT6, macrophages, allergy, asthma

Highlighted Publications

Keegan, A.D., M.P. Beckmann, L.S. Park, and W.E. Paul. 1991. The Interleukin-4 receptor: Biochemical characterization of IL-4-binding molecules in a T cell line expressing large numbers of receptors.  J. Immunol. 146: 2272-2279.

Keegan, A.D., K. Nelms,  M. White, L-M. Wang, J.H. Pierce, and W.E. Paul. 1994. An IL-4 receptor region containing an insulin receptor motif is important for IL-4 mediated IRS-1 phosphorylation and proliferation. Cell. 76:811-820.

Kelly-Welch, A.E., Melo, M.E.F., Ford, A., Noben-Trauth, N., Smith, E., Haudenschild, C., and Keegan, A.D. 2004. Complex Role of the IL-4R-alpha in a murine model of airway inflammation: Expression of the IL-4R-alpha on a non-lymphocytic cell of hematopoietic origin contributes to severity of inflammation. J. Immunol. 172: 4545-55.

Porter, H.A., Perry. A., Kingsley. C., Tran. N.L, and Keegan, A.D. 2013. IRS-1 is highly expressed in estrogen receptor a positive breast tumors and regulates the sensitivity of breast cancer cells to chemotherapy, while IRS-2 is expressed in high grade, invasive breast tumors. Cancer Letters. 338(2): 239-48. NIHMS 472531

Dasgupta, P., Dorsey, N.J.,Li, J.,Qi, X., Smith, E.P., and Keegan, A.D. 2016. Insulin Receptor Substrate (IRS)-2 negatively regulates alternative macrophage activation and allergic lung inflammation. Science Signaling. 9(433):ra63. doi: 10.1126/scisignal.aad6724.

Additional Publication Citations

Wang, H.Y., Paul, W.E., and Keegan, A.D. 1996. IL-4 function can be transferred to the IL-2 receptor by tyrosine containing sequences found in the IL-4 receptor-alpha chain. Immunity. 4: 113-121.

Zamorano, J., Wang, H.Y., Wang, L-M., Pierce, J.H., and Keegan, A.D. 1996. IL-4 protects cells from apoptosis via the insulin receptor substrate pathway and a second independent signaling pathway. J. Immunol. 157: 4926-4934.

Wang, H.Y., Zamorano, J., Yoerkie, J.,  Paul, W.E., and Keegan, A.D. 1997. IL-4-induced tyrosine phosphorylation of IRS is dependent upon expression of JAK-1 in human fibrosarcoma cells. J. Immunol. 158:1037-1040.

Wang, D.Z., Zamorano, J., Keegan, A.D., and Boothby, M.R. 1997. HMG-I(Y) phosphorylation status as a nuclear target regulated through IRS1 and the I4R motif of the IL-4 receptor. J. Biol. Chem. 272: 25083-90.

Zamorano, J., Wang, H.Y., Wang, R., Shi, Y., Longmore, G.D., and Keegan, A.D. 1998. Regulation of cell growth by IL-2: Role of STAT5 in protection from apoptosis but not in cell cycle progression. J. Immunol. 160:3502-3512.

Zamorano, J. and Keegan, A.D. 1998. Regulation of apoptosis by tyrosine-containing domains of the IL-4R-alpha: Y497 and Y713, but not the STAT6-docking tyrosines, signal protection from apoptosis. J. Immunol. 161:859-67.

Wang, H.Y., Zamorano, J. and Keegan, A.D.  1998. A role for the I4R-motif of the IL-4R-alpha in regulating activation of the IRS2 and STAT6 pathways: Analysis by mutagenesis. J. Biol. Chem. 273:9898-9905.

Wang, H. Y., Shelburne, C. P., Zamorano, J., Kelly, A. E., Ryan, J. J., and Keegan, A. D. 1999. Effects of an allergy-associated mutation in the huIL-4R-alpha (Q576R) on huIL-4-induced signal transduction. CUTTING EDGE. J. Immunol. 162: 4385-4389. 

Mora, A., Youn, J.H., Keegan, A.D., and Boothby, M.R. 2001. NFkappa b/Rel participation in the lymphokine-dependent proliferation of T cells. J. Immunol. 166: 2218-27.

Zamorano, J., Kelly, A.E., Austrian, J., Wang, H.Y., and Keegan, A.D. 2001. Costimulation of resting B lymphocytes alters the IL-4-activated IRS-2 signaling pathway in a STAT6 independent manner: Implications for cell survival and proliferation. Cell Research. 11: 44-54.

Hanson, E.M., Dickensheets, H., Qu, C.K., Donnelly, R.P., and Keegan, A.D. 2003. Regulation of the de-phosphorylation of STAT6: Participation of Y713 in the IL-4R-alpha, the tyrosine phosphatase SHP-1, and the proteasome. J. Biol. Chem. 278: 3903-3911.

Moreno, J., Kazcmarek, M.,  Keegan, A.D., and Tondravi, M. 2003. IL-4 suppresses both osteoclast development and mature osteoclast function by a STAT6-dependent mechanism: Irreversible inhibition of the differentiation program activated by RANKL. Blood. 102:1078-86.

Moreno, J.L., Mikailenko, I., Tondravi, M., and Keegan,  A.D. 2007. IL-4 promotes the formation of functional multi-nucleated giant cells from macrophage precursors by a STAT6-dependent mechanism. J. Leuk. Biol. 82: 1542-1553.

Carey, G.B., Semenova, E., Qi, X., and Keegan, A.D. 2007. IL-4 protects the B-cell lymphoma cell line CH31 from anti-IgM-induced growth arrest and apoptosis: Contribution of the PI-3’kinase/Akt pathway. Cell Res. 17: 942-955.

LaPorte, S.L., Juo, J.S., Vaclavikova, J., Colf, L., Qi, X., Heller, N.M., Keegan, A.D., and Garcia, K.C. 2008. Molecular basis of cytokine receptor pleiotropy in the Interleukin-4/13 system. Cell. 132: 259-272. PMCID: PMC2265076.

Heller, N.M., Qi, X., Juntilla, I., Shirey, K.A., Vogel, S.N., Paul, W.E., and Keegan, A.D. 2008. Type I IL-4 Receptors Selectively Activate IRS-2 to Induce Target Gene Expression in Macrophages. Science Signaling. 1: 51, ra17. PMC2739727.

Ford, A.Q., Dasgupta, P., Mikhailenko, I., Smith, E.P., Noben-Trauth, N., and Keegan, A.D. 2012. Adoptive transfer of IL-4R-alpha+ macrophages is sufficient to support Th2-driven alternative macrophage activation and to enhance eosinophilic     inflammation in a mouse model of allergic lung inflammation. BMC-Immunol. Jan. 31 13: 6. PMCID: PMC3118960.

Nkyimbeng-Takwi, E.H., Shanks, K., Smith, E., Iyer, A., Lipsky, M., DeTolla, L., Kikutani, H., Keegan, A.D. and Chapoval, S.P. 2012. A critical functional role for neuroimmune semaphorin 4A in the experimental asthma severity. Mucosal Immunology. 5(4): 409-19. PMC3378810

Dorsey, N.J., Chapoval, S.P., Smith E. P., Skupsky, J., Scott, D.W., and Keegan, A.D. 2013. STAT6 controls the number of regulatory T cells in vivo thereby regulating allergic lung inflammation.  J. Immunol. 191(4):1517-28. PMCID: PMC3735779

Dasgupta, P., Qi, X., Smith, E.P., and Keegan, A.D. 2013. Absence of the common gamma chain (gamma C), a critical component of the Type I IL-4 receptor, increases the severity of allergic lung inflammation driven by adoptively transferred TH2 cells. PLoS ONE. 8(8):e71344. PMCID: PMC3734063

Keegan, A.D., Shirey, K.A., Bagdure, D. Blanco, J., Viscardi, R.M., and Vogel, S.N. 2016. Enhanced allergic responsiveness after early childhood infection with respiratory viruses: Are long-lived alternatively-activated macrophages the missing link? Pathogens and Disease. 74(5). pii: ftw047. doi: 10.1093/femspd/ftw047.