| About Dr. Alex Y. Huang, MD, PhD Dr. Huang received a B.S. in chemistry and an M.S. in biochemistry and molecular biology from the University of Chicago. He then entered the medical scientist training program at the Johns Hopkins University School of Medicine where he completed his Ph.D. thesis in the laboratory of Drew M. Pardoll, M.D., Ph.D. Dr. Huang’s Ph.D. thesis included studying the process of in vivo tumor-antigen cross-presentation by bone marrow derived professional antigen presenting cells and identified the dominant MHC class-I restricted tumor rejection antigen, AH-1, in a murine colon tumor model. After completing pediatric residency at Johns Hopkins Hospital, Dr. Huang entered the combined pediatric hematology/oncology clinical fellowship training program at Johns Hopkins Hospital and the National Cancer Institute. While a postdoctoral fellow in the laboratory of Dr. Ronald N. Germain in the Laboratory of Immunology at NIAID, Dr. Huang received the Cancer Research Institute Postdoctoral Fellowship Award and was among the first to develop the new technique of intravital 2-photon laser scanning microscopy in studying immune cell migration and interaction in secondary lymphoid organs and the gastrointestinal track in vivo. In 2006, Dr. Huang joined the Case Western Reserve University School of Medicine faculty as an Assistant Professor in the Division of Pediatric Hematology / Oncology at Rainbow Babies & Children’s Hospital - Rainbow / Ireland Cancer Center with a secondary faculty appointment in the Department of Pathology and Biomedical Engineering, and an associate membership in the Case Comprehensive Cancer Center. Currently, Dr. Huang is also the director of clinical fellowship program in Pediatric Hematology / Oncology. Dr. Huang was promoted to Associate Professor in 2012.
Dr. Huang’s laboratory research program is focused on adapting intravital 2-photon laser scanning microscopy to study various aspects of in vivo immunity and pathogenesis. These efforts include investigating the role of tumor microenvironment in immune cell recruitment and tolerance induction, interplay between chronic inflammatory conditions with carcinogenesis of the gastrointestinal track, regulation of T cell receptor activation by inflammatory chemokines, and mechanisms of pathogenic lymphocyte recruitment induction in animal models of multiple sclerosis.
Academic Appointment: Case Western Reserve University School of Medicine / University Hospitals Case Medical Center / Rainbow Babies & Children's Hospital Associate Professor, Department of Pediatrics Clinical Fellowship Director,Division of Pediatric Hematology / Oncology Secondary Faculty, Department of Pathology; Department of Biomedical Engineering Member, Case Comprehensive Cancer Center
Member, CWRU MSTP Steering Committee Education & Employment 1986-1990 B.S. with Honors, Department of Chemistry, The University of Chicago, Chicago, IL
1988-1990 M.S., Biochemistry and Molecular Biology Program, The University of Chicago, Chicago, IL
1990-1997 M.D, Johns Hopkins University School of Medicine, Baltimore, MD
1990-1997 Ph.D., Biochemistry, Cellular & Molecular Biology Program, Johns Hopkins U., Baltimore, MD
1997-2000 Pediatric Resident, Department of Pediatrics, Johns Hopkins Hospital, Baltimore, MD
2000-2003 Clinical Fellow, Pediatric Hematology/Oncology, Johns Hopkins Hospital/National Cancer Institute, MD
2003-2006 Postdoctoral Fellow, Lymphocyte Biology Section, Laboratory of Immunology, NIAID, NIH, Bethesda, MD
2006-current Assistant Professor, Department of Pediatric
2007-current Fellowship Director; Rainbow Babies & Children’s Hospital / Case Western Reserve University SOM, Cleveland, OH
2012-current Associate Professor, Departments of Pediatrics and Pathology
State Medical Licensure State Medical Board of Ohio Maryland Board of Physician Quality Assurance Specialty Board 2000-2007 Board Certified, American Academy of Pediatrics 2009-2015 Board Certified, Pediatric Hematology / Oncology 2007-2014 Board Re-certification, American Academy of Pediatrics Professional Society
1992-1997 American Medical Association
1997-2001 American Board of Pediatrics 2004-2005 American Society of Cell Biology 2007-current American Society of Pediatric Hematology Oncology
2011-current American Association of Immunologists (AAI)
2011-current American Society of Clinical Oncology (ASCO)
Funding History
1990-1997 Medical Scientist Training Program, Johns Hopkins University School of Medicine 2001-2003 T32 Research Training Grant, JHH/NIH 2003-2006 Postdoctoral Fellowship Award, Cancer Research Institute, New York, NY 2007-2008 American Cancer Society Institutional Research Grant #IRG-91-022-12 2007-2010 Dana Foundation, New York, NY 2007-2011 Investigator Award, Cancer Research Institute, New York, NY 2008-2013 K12 Career Development Award, Department of Pediatrics, CWRU 2008-2011 Medical Research Award, Gabrielle's Angel Foundation, New York, NY 2008-2011 St. Baldrick's Foundation Career Development Award 2008-2009 Hyundai Motors of America "Hope-on-Wheels" Scholar Program 2010-2011 National Stem Cell & Regenerative Medicine Center Pilot Grant 2011-2012 Case Comprehensive Cancer Center Imaging Pilot Grant 2011-2016 NIH / National Cancer Institute R01 2011-2013 NIH / National Institute of Allergy & Infectious Diseases R21 2011-2013 St. Baldrick's Foundation Career Development Award Extension Grant
2012-2014 Alex's Lemonade Stand Foundation Innovator Award
2012-2014 NIH / National Cancer Institute R01 Diversity Supplement Award
Honors & Awards 1989 Richter Undergraduate Research Scholar, The University of Chicago
1990 Sigma Xi Scientific Research Award, The University of Chicago
1990 Sigma Xi Research Society
1990 Phi Beta Kappa
1990 Undergraduate Research Science Award, The University of Chicago
1996 The Michael A. Shanoff Research Award, Johns Hopkins University School of Medicine
1997 David E. Rogers, M.D. Award, Johns Hopkins University School of Medicine
1998 Junior Achievement Award, NIH-FDA Chinese American Association
2003 Honorable Mention, Fellow Research Day Poster Session, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
2003 Award for Best Light Microscopy Presentation, Chesapeake Society for Microscopy, MD
2005 Fellows Award for Research Excellence (FARE), National Institutes of Health, Bethesda, MD
2005 Top Poster Submission, Cancer Vaccines 2005, International Cancer Immunotherapy Symposia Series, Cancer Research Institute, New York, NY
2007 Honorable Mention, Best Cytokine Research Paper of the Year, NIH Cytokine Interest Group, National Institutes of Health, Bethesda, MD 2008 Sutherland Award for Young Investigators Presentation, Midwest Society for Pediatric Research, Cleveland, OH 2011 Fellows Teaching Award, Rainbow Babies & Children's Hospital, Cleveland, OH
Publications 1. Yang, N.-C.C., Huang, A., Yang, D.-D.H. Photo-dehalogenation of 4-haloindole. J. Am. Chem. Soc. 111: 8060-8061, 1989
2. Huang, A.Y.C., Golumbek, P., Ahmadzadeh, M., Jaffee, E., Pardoll, D., Levitsky, H. Bone marrow-derived cells present MHC class I-restricted tumour antigens in priming of antitumour immune responses, Vaccines against virally induced cancers. Wiley, Chichester. 187: 229-244, 1994. 3. Huang, A.Y.C., Golumbek, P., Ahmadzadeh, M., Jaffee, E., Pardoll, D., Levitsky, H. Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science 264: 961-965, 1994. 4. Wu, T.-C., Huang, A.Y.C., Jaffee, E.M., Levitsky, H.I., Pardoll, D.M. A reassessment of the role of B7-1 expression in tumor rejection. J. Exp. Med. 182: 1415-1421,1995. 5. Woods, A.S., Huang, A.Y.C., Cotter, R., Pasternack, G.R., Pardoll, D.M., Jaffee, E.M. Simplified high sensitivity sequencing of MHC class I-immunoreactive peptides using matrix assisted laser desorption/ionization mass spectrometry. Analytical Biochem. 226: 15-25,1995.
6. Wu, T.-C., Ling, Y., Kanayama, M.D., Huang, A.Y.C., Kurman, R.J. Localization of Epstein-Barr virus-encoded small RNA-1 by in situ reverse transcription: Demonstration of cDNA generation in formalin-fixed paraffin-embedded tissue sections. J. Biomedical Sci. 2: 249-255, 1995.
7. Huang, A.Y.C., Gulden, P., Woods, A.S., Thomas, M.C., Pasternack, G., Cotter, R., Hunt, D., Pardoll, D.M., Jaffee, E.M. The immunodominant MHC class I-restricted antigen of a murine colon tumor derives from an endogenous retroviral gene product. Proc. Natl. Acad. Sci. USA 93: 9730-9735, 1996.
8. Huang, A.Y.C., Bruce, A.T., Pardoll, D.M., Levitsky, H.I. In vivo cross-priming of MHC class I-restricted antigens requires the TAP transporter. Immunity 4: 349-355, 1996.
9. Huang, A.Y.C., Bruce, A.T., Pardoll, D.M., Levitsky, H.I. Does B7-1 expression confer antigen presenting cell capacity to tumors in vivo. J. Exp. Med. 183: 769-776, 1996.
10. Jaffee, E.M., Thomas, M.D., Huang, A.Y.C., Hauda, K.M., Levitsky, H.I., Pardoll, D.M. Enhanced immune priming with spatial distribution of paracrine cytokine vaccines. J. Immunotherapy 19: 176-183, 1996.
11. Chang, E.Y., Chen, C.H., Ji, H., Wang, T.L., Hung, K., Lee, B.P., Huang, A.Y., Kurman, R.J., Pardoll, D.M., Wu, T.-C. Antigen-specific cancer immunotherapy using a GM-CSF secreting allogeneic tumor cell-based vaccine. Int. J. Cancer 86: 725-730, 2000.
12. Huang, A.Y.C., Rigby, M.R. The immune response: Generation, regulation, and maintenance, Immunologic Disorders in Infants and Children. Edited by Steihm, E.R., Ochs, H.D., and Winkelstein, J.A. Saunders Publishing, 5th edition, 2004.
13. Huang, A.Y.C., Qi, H., Germain, R.N. Illuminating the landscape of in vivo immunity: insights from dynamic in situ imaging of secondary lymphoid tissues. Immunity 21:331-339, 2004.
14. Germain, R.N., Castellino, F., Chieppa, M., Egen, J., Huang, A.Y., Koo, L., Qi, H. An extended vision for dynamic high-resolution intravital immune imaging. Seminars in Immunology 17 (6): 431-441, 2005.
15. Castellino, F.*, Huang, A.Y.*, Altan-Bonnet, G., Stoll, S., Scheinecker, C., Germain, R.N. Chemokines enhance immunity by guiding naïve CD8+ T cells to sites of CD4+ T cell-dendritic cell interaction. Nature 440 (7086): 890-895, 2006 (*shared first authorship).
16. Bajenoff, M., Breart, B., Huang, A.Y.C., Qi, H., Braud, V., Germain, R.N., and Glaichenhaus, N. Natural killer cell behavior in lymph nodes revealed by static and real-time imaging. J. Exp. Med. 203 (3): 619-631, 2006.
17. Qi, H., Egen, J.G., Huang, A.Y.C., Germain, R.N. Extrafollicular B lymphocyte activation of lymph nodes by antigen-bearing dendritic cells. Science 312 (5780): 1672-1676, 2006.
18. Chieppa, M., Rescigno, M., Huang, A.Y., Germain, R.N. Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR-engagement. J. Exp. Med. 203:2841-2852, 2006.
19. Huang, A.Y. Watching Immune Cells in Action. Biol. Blood Marrow Transplant 13:111-114, 2007.
20. Guarda, G., Hons, M., Soriano, S.F., Huang, A.Y., Polley, R., Martin-Fontecha, A., Stein, J.V., Germain, R.N., Lanzavecchia, A., Sallusto, F.: L-selectin-negative CCR7- effector and memory CD8+ T cells enter reactive lymph nodes and kill dendritic cells. Nature Immunology 8:743-752, 2007.
21. Bajenoff, M., Egen, J.G., Qi, H., Huang, A.Y., Castellino, F., Germain, R.N.: Highways, Byways, and Breadcrumbs: directing lymphocyte traffic in the lymph node. Trends in Immunology 28:346-35352, 2007. 22. Germain, R.N., Bajenoff, M., Castellino, F. Chieppa, M., Egen, J.G., Huang, A.Y., Ishii, M., Koo, L.Y., Qi, H.: Making friends in out-of-the-way places: how cells of the immuen system get together and how they conduct their business as revealed by intravital imaging. Immunological Reviews 221:163-181, 2008. 23. Tong, C., Barkauskas, D., Nthale, J., Bays, E., Su, C., Liou, H.-L.R., Huang, A.Y.: Visualizing Dynamic Immune Cell Interaction and Function with Two-photon Microscopy. Proceedings Microscopy & Microanalysis 14:152-153, 2008. 24. Huang AY. Bulging glands? Blame it on B cells. Blood. 2010: 115(23)4624-4626.25. Myers J, Huang Y, Wei L, Yan Q, Huang A, Zhou L. Fucose-deficient hematopoietic stem cells have decreases self-renewal and aberrant marrow niche occupancy. Transfusion 2010; 50(12):2660-2669. 26. Simmons DP, Canaday DH, Liu Y, Li Q, Huang A, Boom WH, Harding CV. Mycobacgterium tuberculosis and TLR2 agonists inhibit induction of type I IFN and class I MHC antigen cross processing by TLR9. J. Immunol. 2010; 185(4):2405-2415. 27. Pareek, TK, Lam E, Zheng X, Askew D, Kulkarni AB, Chance MR, Huang AY, Cooke KR, Letterio JJ. Cyclin-dependent kinase 5 activity is required for T cell activation and induciton of experimental autoimmune encephalomyelitis. J. Exp. Med. 2010; 207(11):2507-2519. 28. Lathia JD, Gallagher J, Myers JT, Li M, Vasanji A, McLendon RE, Hjelmeland AB, Huang AY, Rich JN. In vivo evidence for tumor propagation by glioblastoma cancer stem cells. PLoS One. 2011; 6(9):e24807. Epub 2011 Sep 22. 29. Liou HLR, Myers JT, Barkauskas DS, Huang AY. Intravital imaging of the mouse popliteal lymph node. J. Vis. Exp. 2012; Feb 8 (60); pii: 3720. doi:10.3791/3720
30. Huang AY, Myers JT, Barkauskas D, Howell SJ, Oleinick NL, McCormick TS, Cooper KD, Baron ED, Lam M. Cutaneous penetration of the topically applied photosensitizer Pc 4 as detected by intravital 2-photon laser scanning microscopy. Photodiag. Photodyn. Ther. 2012; Sep; 9(3):225-231
31. Mandl JN, Liou R, Klauschen F, Vrisekoop N, Monteiro JP, Yates AJ, Huang AY*, Germain RN*. Quantification of lymph node transit times reveals differences in antigen surveillance strategies of naive CD4+ and CD8+ T cells. Proc. Natl. Acad. Sci. USA. 2012; doi/10.1073/pnas.1211717109.
32. Huang AY, Haining WN, Barkauskas DS, Myers J, Petrosiute A, Garrett AP, Singh K, Cooke K, Kean LS. Viewing Transplant Immunology through Today's Lens: New Models, New Imaging and New Insights. Biol. Blood Marrow Transplant. 2012; doi:pii: S1083-8791 (12) 00436-3. (Epub ahead of print)
Invited Lectures 1. Colorado State University 21st Annual Symposium, Genetic and Therapeutic Aspects of Cancer: What’s on the Horizon? “Development of an antigen-specific tumor vaccine”, CO, February 11, 1995
2. National Taiwan University, “Immunotherapy and cancer vaccine development”, Taipei, Taiwan, May, 1997
3. Changhua Christian Hospital, “Recent development in tumor immunology”, Changhua, Taiwan, May, 1997
4. NIH Immunology Interest Group Retreat, “Two-photon imaging of immune cell interactions and trafficking in vivo”, Airlie, VA, October 20, 2003
5. LI/LCMI Research Seminar, “Dynamic in situ imaging reveals the impact of self and foreign antigens on DC-T cell interactions”, NIH, Bethesda, MD, September 30, 2004
6. NIH Immunology Interest Group Retreat, “Impact of self and foreign antigens on DC-T cell interactions as revealed by dynamic in situ two-photon imaging”, Airlie, VA, October 13, 2004
7. Emory University, “Dynamic in situ imaging of immunity: impact of self and foreign antigens on DC-T cell interactions”, Atlanta, GA, November 17, 2004
8. Pediatric Oncology Branch Friday Morning Seminar Series, NIH, “Dynamic in situ imaging of immunity”, Bethesda, MD, December 3, 2004
9. The American Society for Cell Biology 44th Annual Meeting, Minisymposium on Cell Biology of the Immune System, “Impact of self and foreign antigen recognition on T cell interactions with dendritic cells as revealed by dynamic in situ two-photon imaging”, Washington, DC, December 5, 2004
10. Basic Aspects of Tumor Immunology II, Keystone Symposia, “Imaging immune cell function in situ”, Keystone, CO, March 21, 2005
11. China Medical University & Hospital, “Imaging immune cell function in situ”, Taichung, Taiwan, July 15, 2005
12. Changhua Christian Hospital, “Imaging immune cell function in situ: Visualizing chemokine-guided recruitment of naïve CD8+ T cells to sites of antigen-dependent CD4+ T cell – dendritic cell interaction”, Chuanghua, Taiwan, July 19, 2005
13. NIH Immunology Interest Group Retreat, “Visualizing chemokine-guided recruitment of naïve CD8+ T cell to sites of antigen-dependent CD4+ T cell – dendritic cell interaction in situ”, Airlie, VA, September 21, 2005
14. Cancer Vaccines 2005 - The Next Decade: A Report from the World, Plenary “Visualizing inflammatory chemokine-guided recruitment of naïve CD8+ T cells to sites of antigen-dependent CD4+ T cell – dendritic cell interactions in situ”, New York, NY, October 5, 2005
15. Food & Drug Administration, “Visualizing immunity in situ”, Bethesda, MD, December 16, 2005
16. Scanning 2006, Plenary “Dynamic high resolution imaging of immune cell behavior using intra-vital two-photon microscopy”, Washington, DC, April 25, 2006
17. BMT Tandem Meeting 2007, Plenary: “Watching immune cells in action”, Keystone, Colorado. February 9, 2007
18. 22nd Annual Congress of the European Association of Urology, Plenary: “Imaging of immune cells trafficking”, Berlin, Germany. March 23, 2007
19. Anti-Tumor Immunotherapies, Keystone Symposia, “Chemokine Guidance of Cellular Cooperation During Primary Adaptive Immune Response”, Banff, Canada, March 31, 2007
20. New Faculty Symposia, Case Western Reserve University School of Medicine, “A Picture Tells a Thousand Words: Dynamic High Resolution Imaging of Immune Cellular Cooperation In Vivo”, Cleveland, Ohio. April 18, 2007
21. Case Comprehensive Cancer Center Annual Retreat, Program 6, “DynamicSingle-cell Imaging In Situ”, Painesville, Ohio. July 14, 2007
22. Department of Medical Microbiology & Immunology / Infection, Immunity & Transplantation Seminar, University of Toledo Health Science Campus, “Visualizing Immune Cellular Trafficking and Response In Situ”, Toledo, Ohio. September 12, 2007
23. Molecular Pathology Seminar Series, Johns Hopkins University School of Medicine, “Close Encounter of the Right Kind: Understanding Immune Response in Tissue Milieu”, Baltimore, Maryland. October 17, 2007
24. Immunology Seminar Series, Case Western Reserve University School of Medicine, “Dynamic Imaging of Immune Cell Behavior In Situ”, Cleveland, Ohio. October 30, 2007 25. 2008 Rammelkamp Research Conference, the MetroHealth System, "Imaging Dynamic Immune Cell Behavior In Situ", Cleveland, Ohio. February 28, 2008 26. CWRU Biomathematical Forum, "Measuring Dynamic Cellular Behavior In Vivo", Cleveland, Ohio. April 25, 2008 27. Microscopy & Microanalysis 2008, Structural Basis of Disease, “Visualizing Dynamic Immune Cell Interaction and Function with Two-photon Microscopy”, Albuquerque, NM. August 7, 2008. 28. Immunotherapy in Pediatric Oncology: Progress and Challenges, "Regulation of inflammatory Chemokine Receptor, CCR5: Its Role in Naive T Cell Memory Generation and Tumor Rejection", National Cancer Institute, Bethesda, MD. September 10, 2008. 29. Department of Pharmacology Seminar Series, "Role of Inflammatory Chemokines in Naive T Cell Activation and Tumor Rejection", Case Western Reserve University, September 16, 2008. 30. Midwest Society for Pediatric Research 49th Annual Meeting, "Role of Chemokine Receptor CCR5 on Naive T Cell for Memory Formation and Tumor Rejection", Cleveland, OH. October 16, 2008. 31. Child Health Research Center Annual Retreat, "Role of Inflammatory Chemokines in T Cell Memeory Generation and Tumor Rejection as Revealed by Real-time 2-photon Microscopy", National Institute of Child Health and Human Development (NICH). The Woodlands, Texas. November 7, 2008. 32. Department of Immunology Seminar Series, "Orchestrating Adaptive Immunity with Inflammatory Chemokines: Visualizing In Vivo Immunity with 2-Photon Microscopy", National Jewish Medical and Research Center. Denver, CO. November 19, 2008.
(last updated 12/2008)
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