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Huang Laboratory at Case Western Reserve University School of Medicine

Discovering Immunity in Health & Disease. Finding Cures for Childhood Cancer.

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                                                    This page was last modified on Monday, December 11, 2017 06:09:21 PM

                                 
Welcome to the

Huang Lab

at

Case Western Reserve University School of Medicine 
 
Principal Investigator

Alex Y. Huang, MD, PhD
Professor of Pediatrics
Secondary Appointments in Pathology, BME and General Medical Sciences

 
Case Western Reserve University
Angie Fowler AYA Cancer Institute
University Hospitals Cleveland Medical Center
Rainbow Babies & Children's Hospital
Cleveland, Ohio USA


Upcoming Seminar / Conference Engagement:
  • Rowley Scientific Symposium, U. of Chicago, May 19, 2017
  • Pathology Retreat, Albert Einstein College of Medicine, May 29-30, 2017
  • Taipei Medical University, June 30, 2017
  • The Scientist Webinar, July 19th, 2017
  • 3rd International Cancer Immunotherapy Symposium, Mainz, Germany, September 9, 2017
  • NANETS Conference, October 19, 2017 (Dr. Petrosiute)
  • Capitol Hill Forum on Pediatric Immunotherapy, October 25, 2017
  • Gabrielle Angel Foundation Symposium, November 6-7, 2017
  • Vaccine R&D Conference, Washington DC, November 15-17, 2017
  • 2nd Global AYA Cancer Congress, Atlanta, GA, December 5, 2017
  • BMT-Tandem, Salt Lake City, Utah, February 2018
  • TRCCC Immunotherapy Conference, Seven Springs, PA, February 14-16, 2018
  • Gordon Conference, March 25, 2018
  • BIRS Quantitative Immunology, Oaxaca, Mexico, June 24-29, 2018

Huang Lab Photos
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Focus of our laboratory:

        Regulation between immune activation and tolerance is crucial in the pathogenesis of cancer. Recent development of intravital 2-photon microscopy allows direct observation of how immune cells traffic and interact with various cells in the tumor micro-environment in real time with single-cell resolution.

       Our laboratory is interested in applying this and other classical immunological techniques to study various aspects of anti-tumor immune responses, immune – host – pathogen interaction, T cell-mediated memory immunity, and chemokine - receptor biology.  Ongoing projects include:
 
1) Investigation into factors which influence the dynamic recruitment of T cells and their interactions with tumor cells and associated antigen-presenting cells in tumor-associated micro-environment
 
2) Imaging dynamic interaction between peri-vascular APC and T cells in the CNS during induction of acute experimental autoimmune encephalomyelitis
 
3) Discovering molecular signaling mechanisms responsible for the regulation of chemokine receptor expression on naive T cells
 
4) Testing the efficacy of genetically-modified tumor vaccines in the setting of sarcomas and other childhood cancer

5) Developing imaging techniques to interrogate immune cell migration and interactions in tissues such as the bone marrow, lung, GI track and the skin.

6) Cellular and molecular mechanisms of metastasis in osteosarcoma, rhabdomyosarcoma and other common AYA and childhood cancer. 

7) Mechanisms of immune checkpoint regulation in solid tumors.  

8) Molecular mechanisms of T-cell Leukemogensis and CNS metastasis.

9) Exploring NK cell-based immunotherapy strategies against common pediatric and AYA cancers.

The long-term goal of our laboratory is to translate insights gained from basic investigations of in vivo immunity into rationally designed tumor vaccine and immunotherapeutic clinical trials, with a particular emphasis in the areas of pediatric sarcomas and other solid tumors in the pediatric and adolescent & young adult (AYA) populations.  
  

Recent Publications: (My NCBI)


2017

Dorand RD, Petrosiute A, Huang AY. Multifactorial regulator of tumor PD-L1 response. Transl. Cancer Research 2017. In press.


Allen F, Bobanga I, Rauhe P, Barkauskas D, Teich N, Tong C, Myers J, Huang AY. CCL3 augments tumor rejection and enhances CD8+ T cell infiltration through NK and CD103+ dendritic cell recruitment via IFNgamma. OncoImmunology 2017. In press.


Allen F, Myers J, Tong AA, Rauhe P, Nathle J, Eid S, Huang AY. CCL3 augments antitumor immune priming in the tumor draining lymph node. Frontiers in Immunology 2017. In press.


Zhang M, Chun L, Sandoval V, Graor H, Myers J, Nthale J, Rauhe P, Senders Z, Choong K, Huang AY, Kim J. Systemic administration of beta-glucan of 200 kDa modulates melanoma microenvironment and suppresses metastatic cancer. OncoImmunology 2017. In press.


Wang W, Yu S, Myers J, Wang Y, Xin WW, Alkabri M, Xin AW, Li M, Huang AY, Xin W, Siebel CW, Lazarus HM, Zhou L. Notch2 blockade enhances hematopoietic stem cell mobilization and homing. Haematological 2017; doi: 10.3324/haematol.2017.168674 ]Epub ahead of print]


Rathkey JK, Benson BL, Chirieleison SM, Yang J, Xiao TS, Dubyak GR, Huang AY, Abbott DW. Live cell visualization of gasdermin D-driven pyroptotic cell death. J Biol Chem 2017; doi: 10.1074/jbc.M117.797217 [Epub ahead of print]


Tong AA^, Hashem H^, Eid S, Huang AY. Adoptive natural killer cell therapy is effective in reducing pulmonary metastasis of Ewing Sarcoma. OncoImmunology 2017; 6(4): e1303586 (^co-first authors)


Chung J, Ebens CL, Radojcic V, Perkey E, Koch U, Scarpellino L, Tong A, Allen F, Wood S, Feng J, Friedman A, Granadier D, tran IT, Chai Q, Onder L, Yan M, Reddy P, Blazar BR, Huang AY, Brennan TV, Bishop DK, Ludewig B, Siebel CW, Radtke F, Luther SA, Maillard I. Fibroblastic niches prime T cell alloimmunity through Delta-like Notch ligands. J. Clinical Investigation 2017; 127(4):1574-1588.


Shukla S, Myers JT, Wood SE, Gong X, Czapar AE, Commandeur U, Huang AY, Levine A, Steinmetz NF. Plant viral nanoparticules-based HER2 vaccine: Immune response influenced by differential transport, localization and cellular interactions of particulate carriers. Biomaterials 2017; 121:15-27.


Askew D, Pareek T, Eid S, Ganguly S, Tyler AY, Letterio JJ, Cooke KR. Cyclin-dependent kinase 5 (Cdk5) activity is required for generation of allogeneic T cell responses after hematopoietic cell transplantation in mice. Blood 2017; 129(2): 246-256.


Wilkerson A, Kim J, Huang AY, Zhang M. Nanoparticle systems modulating myeloid-derived suppressor cells for cancer immunotherapy. Current Topics in Medicinal Chemistry 2017; 17(16): 1843-1857.


2016

Metheny L, Eid S, Lingas K, Reese J, Meyerson H, Tong A, de Lima M, Huang AY. Intra-osseous co-transplantation of CD34-selected umbilical cord blood and mesenchymal stromal cells. Hematology & Medical Oncology 2016. 1(1): 41-45.


Dorand RD, Nthale J, Myers JT, Barkauskas DS, Avril S, Chirieleison SM, Pareek TK, Abbott DW, Stearns DS, Letterio JJ, Huang AY^, Petrosiute AY^ Cdk5 disruption attenuates tumor PD-L1 expression and promotes anti-tumor immunity. Science 2016. 353(6297): 399-403 (^co-senior authors).


Allen F^, Tong AA^, Huang AY. Unique transcompartmental bridge: antigen-presenting cells sampling across endothelial and mucosal barriers. Frontiers in Immunology 2016. 7:231. doi: 10.3369/fimmu.2016.00231 (^co-first author)


Shukla S^, Dorand RD^, Myers JT, Wood SE, Gulati NM, Stewart P, Commandeur U, Huang AY*, Steinmetz NF* Multiple administration of viral nanoparticles alter in vivo behavior - insights from intravital microscopy. ACS Biomaterials Science and Engineering 2016; 2(5): 829-837. (^co-first authors; *co-senior and co-corresponding authors)


Askew D, Su C, Liou R, Barkauskas D, Dorand RD, Myers JT, Nthale J, Huang AY. Transient surface CCR5 expression by naive CD8+ T cells within inflamed lymph nodes is dependent on HEV interaction and augments helper T-cell dependent memory response. J. Immunol. 2016; 96(9): 3653-3664.


Wang W, Zimmerman G, Huang X, Myers J, Wang Y, Moreton S, Nthale J, Awadalla A, Beck R, Xin W,  Wald D, Huang AY, Zhou L. Abberant Notch signaling in acute lymphoblastic leukemia marrow suppresses osteoblasts and inhibits hematopietic niche function. Cancer Research. 2016; 76(6): 1641-1652.


2015

Bhaskaran N, Quigley C, Weingerb A, Huang A, Popkin D, Pandiyan P. Transforming growth factor-b1 sustains the survival of FoxP3+ regulatory cells during late phase of oropharyngeal condidiasis infection. Mucosal Immunology 2015; Doi: 10.1038/mi.2015.115 [Epub ahead of print].

Sinyuk M, Alvarado AG, Nesmiyanov P, Shaw J, Mulkearns-Hubert EE, Eurich JT, Hale JS, Bogdanova A, Hitomi M, Maciejewski J, Huang AY, Saunthararajah Y, Lathia JD. Cx25 contributes to leukemia cell communication and chemosensitivity. Oncotarget 2015; 6(31): 31508-31521.

Delvecchio FR, Vadrucci E, Cavalcanti E, De Santis S, Dale K, Vacca M, Myers J, Allen F, Bianco G, Huang AY, Monsurro V, Santino A, Chieppa M. Polypheol administration impairs T-cell proliferation by imprinting a distinct dendritic cell maturation profile. European J. Immunology 2015; 45(9): 2638-2649.

Omenetti S, Brogi M, Goodman WA, Croniger CM, Eid S, Huang AY, Laffi G, Roskams T, Cominelli F, Pazani M, Pizarro TT. Dysregulated intrahepatic CD4+ T-cell activation drives liver inflammation in ileitis-prone SAMP1/YitFc mice. Cellular and Molecular Gastroenterology and Hepatology 2015; 1(4): 406-419.

Wang W, Yu S, Zimmerman G, Wang Y, Myers J, Yu V, Huang D, Huang X, Shim J, Huang Y, Xin W, Qiao P, Yan M, Xin W, Scadden D, Stanley P, Low JB, Huang AY, Siebel CW, Zhou L. Notch receptor - ligand engagement maintains hematopoietic stem cell quiescence and niche retention. Stem Cells 2015; 33(7): 2280-2293.

Barkauskas DS, Dorand RD, Myers JT, Evans TA, Barkauskas KJ, Askew D, Purgert R, Huang AY. Focal transient CNS vessel leak provides a tissue niche for sequential immune cell accumulation during the asymptomatic phase of EAE induction. Experimental Neurology 2015; 266:74-85
(Read the article).

Owusu-Ansah A, Choi SH, Petrosiute A, Letterio JJ, Huang AY. Triterpenoid inducers of Nrf2 signaling as potential therapeutic agents in sickle cell disease - a review. Frontiers of Medicine 2015; 9(1): 46-56.

2014
Dorand RD, Barkauskas DS, Evans TA, Petrosiute A, Huang AY. Comparison of intravital thinned skull and cranial window approaches to study CNS immunobiology in the mouse cortex. Intravital 2014; 3(2): e29728.


Evans TA, Barkauskas DS, Myers JT, Huang AY. Intravital imaging of dynamic axonal interactions with microglia and macrophages in a mouse dorsal column crush injury. J. Vis. Exp. 2014, (93), e52228.

Ravikumar M, Snunil S, black J, Barkauskas DS, Huang AY, Miller RH, Selkirk SM, Capadona JR. Blood-derived macrophages dominate over resident microglia in mediating the neuroinflammatory response to implanted intracortical microelectrodes. Biomaterials. 2014; 35(28): 8049-8064.

Cavalcanti E, Vadrucci E, Delvecchio F, Addabbo F, Bettini S, Liou R, Huang AY, Pizzaro TT, Santino A, Chieppa M. Reconstituted oil bodies polyphenol mix administration efficiently suppress dendritic cell inflammatory pathway and acute intestinal inflammation. PLoS One 2014; 9(2): e88898.

Evans, TA, Barkauskas, DS, Myers J, You, JQ, Hare EG, Ransohoff R, Huang AY*^, Silver J*. High-resolution intravital imaging reveals that blood derived macrophages but not resident microglia facilitate secondary axonal dieback in traumatic spinal cord injury. Experimental Neurology 2014; 254:109-120 (Featured as Journal Cover; *Shared Senior Author; ^Communicating PI).

Scrimieri, F, Askew D, Corn DJ, Eid S, Bobanga ID, Bjelac JA, Tsao ML, Othman YS, Wang SG, Huang AY. Murine Leukemia Virus Envelope Gp70 is a Shared Biomarker for High-sensitivity Detection and Quantification of Murine Tumors. OncoImmunology 2014; 2(11): e26889.

2013
Bodas P, Huang A, ORiordan MA, Sedor JR, Dell KM. The prevalence of Hypertension and Abnormal Kidney Function in Children with Sickle Cell Disease - a Cross Sectional Review. BMC Nephrol. 2013; 14(1):237.

Bobanga ID, Petrosiute A, Huang AY. Chemokines as Cancer Vaccine Adjuvants. Vaccines 2013; 1:444-463.

Barkauskas DS*, Evans TA*, Myers J, Petrosiute A, Silver J, Huang AY. Extravascular CX3CR1+ Cells Extend Intravascular Dendritic Processes intoIntact Central Nervous System Vessel Lumen. Microscopy & Microanalysis 2013; 19(4):778-90.

Myers J, Barkauskas DS, Huang AY. Dynamic imaging of marrow-resident granulocytes interacting with human mesenchymal stem cell upon systemic lipopolysaccharide challenge. Stem Cell International. 2013; 2013:656839.
(Highlighted by Global Medical Discovery... read the article)

2012
Huang AY, Haining WN, Barkauskas DS, Myers J, Petrosiute A, Garrett AP, Singh K, Cooke K, Kean LS. Viewing transplantation immunology through today's lens: new models, new imaging, and new insights. Biol. Blood Marrow Transplant. 2013; 19(1 Suppl): S44-51.

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 (*co-senior authors)

Huan
g AY, Myers JT, Barkauskas D, Howell SJ, Oleinick NL, McCormick TS, Cooper KD, Baron ED, Lam M. Cutaneous penetration of the topically applied photosensitizer Pc4 as detected by intravital 2-photon laser scanning microscopy. Photodiag. Photodyn. Ther. 2012; 9(3): 225-231.

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.

2011

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.
 
2010
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.
 
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.
 
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.
 
Huang AY. Bulging glands? Blame it on B cells. Blood. 2010; 115(23):4624- 4626.
 
2008
Germain RN, Bajenoff M, Castellino F, Chieppa M, Egen JG, Huang AYC, Ishii M, Koo LY, Qi H. Making friends in out-of-the-way places: how cells of the immune system get together and how they conduct their business as revealed by intravital imaging. Immunological Reviews 2008; 221:163-181

2007
Bajenoff M, Egen JG, Qi H, Huang AY, Castellino F, Germain RN. Highways, byways and breadcrumbs: directing lymphocyte traffic in the lymph node. Trends Immunol. 2007, 28(8): 346-352.

Guarda G, Hons M, Soriano SF, Huang AY, Polley R, Martin-Fontecha A, Stein JV, Germain RN, Lanzavecchia A, Sallusto F. L-selectin- CCR7- effector and memory CD8+ T cells enter reactive lymph nodes and kill dendritic cells. Nat. Immunol. 2007, 8(7):743-52.
 
Huang AY. Watching Immune Cells in Action. Biology of Blood and Marrow Transplantation. 2007, 13:111-114.
 
2006
Chieppa M, Rescigno M, Huang AY, Germain RN. Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TCL engagement. J Exp Med. 2006, 203:2841-52.
 
Qi H, Egen JG, Huang AY, Germain RN. Extrafollicular activation of lymph node B cells by antigen-bearing dendritic cells. Science 2006, 312-1672-76.
 
Castellino F*, Huang AY*, Altan-Bonnet G, Stoll S, Scheinecker C, Germain RN. Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell-dendritic cell interaction. Nature 2006, 440:890-95 (*shared first authorship).
 
Bajenoff M, Breart B, Huang AY, Qi H, Cazareth J, Braud VM, Germain RN, Glaichenhaus N. Natureal killer cell behavior in lymph nodes revealed by static and real-time imaing. J Exp Med. 2006, 203:619-31.
 
2005
Germain RN, Castellino F, Chieppa M, Egen JG, Huang AY, Koo LY, Qi H. An extended vision for dynamic high-resolution intravita immune imaging. Semin Immunol. 2005, 17:431-41.
 
2004
Huang AY, Qi H, Germain RN. Illuminating the landscape of in vivo immunity: insights from dynamic in situ imaging of secondary lymphoid tissues. Immunity 2004, 21:331-339.
 
[for a complete list of publications, please see ABOUT US page]

 


Huang Lab NEWS...

October 25, 2017

Dr. Huang spoke at a Senate Briefing on Pediatric Immunotherapy sponsored by St. Baldrick's Foundation and Senators Marco Rubio (R-FL) and Michael Bennet (D-CO). Read the press release.
  

September 2017

Congratulations to Dr. Agne Petrosiute for being awarded a $55,000 Immunotherapy pilot grant from Case Comprehensive Cancer Center.


August 15, 2017

Congratulations to Dr. Yamilet Huerta for receiving a $7500 2017 Fellows Research Award Program (FRAP) fellowship to support her work in Engager T cell work. Great job, Yamilet.



 August 14, 2017

Congratulations to Dr. Stefanie Avril for being awarded a $50,000 Case Comprehensive Cancer Center Pilot Grant entitled, "Identifying the genomic and immunophenotypic underpinnings of racial disparities in endometrial cancers." Great job, Stefanie! 



August 11, 2017

Read the latest blog from St.
Baldrick's Foundation about the recipients of SBF Innovation Award.
.