The Hambardzumyan lab resides in the newly constructed Health Sciences Research Building. The building offers 200,000 square feet of space dedicated to research in drug discovery, immunology and vaccines, neurosciences, cancer, gastroenterology, transplant immunology, nephrology, biomedical engineering, and human genetics.
The Hambardzumyan lab occupies approximately 750 square feet in the HSRB and has bench space to accommodate 4-6 researchers. The lab contains desk space that is separated from the BSL-2 wet lab area by large windows.
Our recent paper discusses the two populations of tumor-associated macrophages in glioblastoma. It shows that bone marrow-derived macrophages are capable of infiltrating the tumor and display significantly different expression profiles than brain-resident microglia.
Genetic Driver Mutations Define the Expression Signature and Microenvironmental Composition of High-Grade Gliomas
Our recent paper outlines the expression profile and microenvironmental composition of our murine tumors driven by PDGFB-overexpression and NF1-silencing. Moreover, this paper demonstrates the relationship between our murine tumors and their human counterparts.
Recent advances in our understanding of glioma biology have elucidated a complex tumor microenvironment consisting of both neoplastic and non-neoplastic cells. These cells communicate through a complex network of cell-cell interactions, cytokines, growth factors, and other signalling molecules thereby driving tumor growth, invasion and treatment resistance. Particularly, tumor-associated macrophages have been shown to constitute a large portion of the microenvironment and are thought to contribute to the treatment-resistant phenotype of high grade gliomas. Therefore, the Hambardzumyan laboratory has taken on the challenge of disecting the role of tumor-associated macrophages in gliomas utilizing genetically engineered mouse models as well as cutting edge imaging techniques, organotypic slice culture, and large scale gene expression analysis. Moreover, through partnerships with other Winship members, the Hambardzumyan lab has performed immunohistochemical and gene expression analysis on human tumor samples. Through this work, the lab hopes to elucidate novel therapeutic targets to allow for the development of pharmaceuticals that target the interactions between neoplastic and non-neoplastic cells of the tumor microenvironment.
Zhihong "Z" Chen, PhD: Z is an instructor working in the Hambardzumyan lab. He received a Master’s degree in Biochemistry from China Pharmaceutical University in Nanjing, China and a PhD degree in Immunology from the University of Ottawa in Ottawa, Canada. He completed a postdoctoral training at the Cleveland Clinic in Cleveland, OH. His research focuses on the innate immunity in various CNS diseases. He had demonstrated that gammadelta T cells are capable of inflicting injuries to brain tissue in multiple sclerosis patients via a cytotoxic mechanism termed “ADCC”. He also showed that microglia, the resident macrophage of the CNS, can protect the brain from traumatic injury. His current work in the lab investigates how peripheral monocytes and CNS microglia differentially contribute to glioblastoma development in relevance to different GBM subtypes. Dr. Z has broad expertise in Neurosciences and Immunology and applies cutting-edge technologies such as 3D electron microscopy, multiphoton microscopy, FACS, and laser-capture microdissection in addressing his scientific questions.
Cameron Herting, BS: Cameron received a BS in Chemistry from Emory University. Following graduation, he matriculated into the Molecular and Systems Pharmacology program where he currently resides as a graduate student. Cameron's research in the Hambardzumyan lab focuses on the functional differences in tumor-associated bone marrow-derived macrophages and microglia related to IL-1 signaling. This research relates to his interest in how dexamethasone alters IL-1 signaling and tumor-associated macrophage activity. He hopes to utilize his expertise in pharmacology to design a novel therapy to treat brain tumor-associated edema. To achieve this goal he utilizes his expertise in primary cell culture, confocal microscopy, MRI, and mouse models of high-grade gliomas.
James Ross, BS: James received his undergraduate degree from Berry College in Georgia. He then started his doctoral training in the Cancer Biology program at Emory University where he currently remains. James is interested in differences between PDGFA and PDGFB driver mutations in glioblastoma. Moreover, his work focuses on histone modifications in pediatric tumors and their functional relevance.
Milota Kaluzova, PhD: Milota received her PhD from the Virological institute, Slovak Academy of Sciences and she received her postdoctoral experience at University of California, Irvine. She is a Research Associate in the Laboratory of Brain Tumor Microenvironment, Department of Pediatrics, Emory University. Her primary interest is an IL-1β pro-tumorigenic signaling loop in glioblastoma.
Ben Gabanic: Ben is a motivated undergraduate at Emory who joined the lab in the fall of 2017. He is a native of Cleveland, Ohio and has aspirations of matriculating into medical school following graduation. Ben has already demonstrated his expertise in tissue processing, brain slicing, immunohistochemistry, immunofluorescence, and image analysis. With his enthusiasm and dedication he has helped contribute to the progress of each of our lab's projects.
Chen Z, Feng X, Herting CJ, Garcia VA, Nie K, Pong WW, Rasmussen R, Dwivedi B, Seby S, Wolf SA, Gutmann DH, Hambardzumyan D. Cellular and Molecular Identity of Tumor-Associated Macrophages in Glioblastoma. Cancer Res. 2017;77(9):2266-78. Epub 2017/02/27. doi: 10.1158/0008-5472.CAN-16-2310. PubMed PMID: 28235764.
Herting CJ, Chen Z, Pitter KL, Szulzewsky F, Kaffes I, Kaluzova M, Park JC, Cimino PJ, Brennan C, Wang B, Hambardzumyan D. Genetic driver mutations define the expression signature and microenvironmental composition of high-grade gliomas. Glia. 2017. Epub 2017/08/25. doi: 10.1002/glia.23203. PubMed PMID: 28836293.
Pan Y, Smithson LJ, Ma Y, Hambardzumyan D, Gutmann DH. Ccl5 establishes an autocrine high-grade glioma growth regulatory circuit critical for mesenchymal glioblastoma survival. Oncotarget. 2017;8(20):32977-89. Epub 2017/04/06. doi: 10.18632/oncotarget.16516. PubMed PMID: 28380429; PMCID: PMC5464843.
Pitter KL, Tamagno I, Alikhanyan K, Hosni-Ahmed A, Pattwell SS, Donnola S, Dai C, Ozawa T, Chang M, Chan TA, Beal K, Bishop AJ, Barker CA, Jones TS, Hentschel B, Gorlia T, Schlegel U, Stupp R, Weller M, Holland EC, Hambardzumyan D. Corticosteroids compromise survival in glioblastoma. Brain. 2016;139(Pt 5):1458-71. Epub 2016/03/30. doi: 10.1093/brain/aww046. PubMed PMID: 27020328; PMCID: PMC5006251.
Hambardzumyan D, Bergers G. Glioblastoma: Defining Tumor Niches. Trends Cancer. 2015;1(4):252-65. Epub 2016/04/19. doi: 10.1016/j.trecan.2015.10.009. PubMed PMID: 27088132; PMCID: PMC4831073.
Feng X, Szulzewsky F, Yerevanian A, Chen Z, Heinzmann D, Rasmussen RD, Alvarez-Garcia V, Kim Y, Wang B, Tamagno I, Zhou H, Li X, Kettenmann H, Ransohoff RM, Hambardzumyan D. Loss of CX3CR1 increases accumulation of inflammatory monocytes and promotes gliomagenesis. Oncotarget. 2015;6(17):15077-94. Epub 2015/05/20. doi: 10.18632/oncotarget.3730. PubMed PMID: 25987130; PMCID: PMC4558137.
Hambardzumyan D, Gutmann DH, Kettenmann H. The role of microglia and macrophages in glioma maintenance and progression. Nat Neurosci. 2016;19(1):20-7. Epub 2015/12/30. doi: 10.1038/nn.4185. PubMed PMID: 26713745; PMCID: PMC4876023.
Hambardzumyan D, Parada LF, Holland EC, Charest A. Genetic modeling of gliomas in mice: new tools to tackle old problems. Glia. 2011;59(8):1155-68. Epub 2011/02/10. doi: 10.1002/glia.21142. PubMed PMID: 21305617; PMCID: PMC3619979.
Bleau AM, Hambardzumyan D, Ozawa T, Fomchenko EI, Huse JT, Brennan CW, Holland EC. PTEN/PI3K/Akt pathway regulates the side population phenotype and ABCG2 activity in glioma tumor stem-like cells. Cell Stem Cell. 2009;4(3):226-35. Epub 2009/03/07. doi: 10.1016/j.stem.2009.01.007. PubMed PMID: 19265662; PMCID: PMC3688060.
Hambardzumyan D, Amankulor NM, Helmy KY, Becher OJ, Holland EC. Modeling Adult Gliomas Using RCAS/t-va Technology. Transl Oncol. 2009;2(2):89-95. Epub 2009/05/05. PubMed PMID: 19412424; PMCID: PMC2670576.
For questions regarding protocols and reagents, please reach out to the relevant lab member at the email addresses below:
Zhihong "Z" Chen: firstname.lastname@example.org
Cameron Herting: email@example.com
James Ross: firstname.lastname@example.org
Milota Kaluzova: email@example.com
April 2018 was highlighted by the acceptance and publication of Z's review paper. It can be found here. We are quite proud of Z for this accomplishment and are excited about the foundation it has laid for the lab to investigate T-cell targeted therapies in glioblastoma. Stay tuned for more information about this project as it develops.
In other news, we are currently in the process of wrapping up a paper by Ioannis Kaffes, a former member of the lab. We will also post more information about this project when it is completed. Until then, we will continue to work hard in the lab and hopefully will provide more exciting results in the coming months.
The month of March 2018 has been great to the Hambardzumyan lab. James received a 9th percentile score on his F31 application and is almost certainly going to be funded. Additionally, Cameron received the notice of award for his F31 application. We all feel very fortunate to be part of such a wonderful group of scientists. Z is in the process of putting the final touches on a review paper regarding the immune microenvironment in glioblastoma. We will post a link once it has been published.
In other news, everyone has been hard at work collecting data for a variety of upcoming papers and grant applications. We are excited about the results of our experiments and are eagerly anticipating sharing them with the rest of the world. Stay tuned for the upcoming updates from the Hambardzumyan Lab!