Dr. Carey is an Assistant Professor in the Department of Microbiology and Immunology. As the Director of Student Summer Research and Community Outreach, Dr. Carey oversees and is responsible for medical student research activities, including electives, summer and year-off activities. He oversees recruitment to and advising for the School of Medicine's summer research programs for health professional, undergraduate and high school students. In his outreach roles within the OSR and as a co-chair on the President's Outreach Council, Dr. Carey explores research, mentoring and STEM (Science Technology Engineering and Math) educational opportunities for students at all levels and from broad backgrounds, on and off the UMB campus. In addition, Dr. Carey is the leader (P.I.) of an NIH/NCI-funded research program focused on increasing the understanding of factors that determine life and death decisions in lymphoma and in other cancers. His teaching activities cover both basic and special topics in immunology and oncology in the Graduate School and the Schools of Medicine and Dentistry. Dr. Carey is a member of the Center for Vascular and Inflammatory Diseases (CVID) and of the Greenebaum Cancer Center.
Our long-range research interests are to explore the mechanism of programmed cell death in tumor cells and especially B-cell lymphomas, via death receptors and by chemotherapeutic agents. We are exploring the notion that controlled oxidation (Reactive Oxygen Species, ROS) can promote the selective targeting, processing and targeted destruction of critical growth and survival proteins. Our research combines multiple molecular, proteomic, metabolomic and fluorescence-based and proteomics-based approaches to potentially target protein kinases in the PI3K/Akt and Ras signaling pathways and to invoke protein phosphatases for the selective killing of lymphomas, prostate and breast cancer cells. Ultimately, gaining better understanding in this area will aid the design or screening of better targeted, more potent and less toxic therapies for the treatment of cancer.
Lab Techniques and Equipment:
RedOx biology, lymphoma, Reactive Oxygen Species, western blotting, Flow cytometry, molecular targeting, biochemistry
Grants & Contracts:
Funding - Active Research Funding Awards & Applications:
P.I. Gregory B. Carey
Agency: NIH/NCI 9/1/2011-08/31/2013 (75% yr 1, 50% Yr 2)
Title: Roles of Reactive Oxygen Species in B Cell Lymphoma Fate.
Major Goals: The major goals of this project is to explore the role of SOD1 and the mechanisms that dynamically regulate this critical RedOx protein in B cell lymphomas.
Award: $275,000 direct.
Total: $412,500 Max/2yrs
P.I. Xi Zhan
Role: Co-P.I. Gregory B. Carey 1.2 calendar (3%)
Agency: NIH/NCI 4/01/2012 - 03/31/2017
Title: The Role of The Missing in Metastasis Gene in Tumor Progression Major Goals: The major goals of this project are to define the role of the Missing in Metastasis gene in B cell lymphoma development and progression.
Major Findings: MIM Depletion leads to spontaneous generation of B cell lymphoma, gut-directed autoantibodies and homing perturbations in lymphocytes and lymphoma.
Award Totals: Direct: $1,250,000.
P.I. Gregory B. Carey
Agency: NIA 8/1/2013-7/31/2014 (10%)
Title: Short-term Training Program on Aging Major Goals: The major goals of this training grant are to introduce health professional students (Medical, Dental, Pharmacy and Physical Therapy students) to research and specifically, research as it relates to aging. Students are competitively selected and matched with mentors. The program runs 10 weeks every summer.
Award: $~143,000/year to support 20 students.
P.I. Gregory B. Carey
Agency: NIH/NCI 4/1/2014-3/31/2016 (50% yr 1, 50% Yr 2)
Title: Exploring B Cell Receptor Driven Autophagy and Mitophagy In Lymphoma Major Goals: The major goals of this project are to explore the mechanisms of B cell receptor stimulated autophagy and mitophagy responses and to determine the roles of those processes in life and death decisions in lymphoma.
Award: $275,000 direct.
Total: $412,500 Max/2yrs
Funding - Completed Research Funding Awards & Applications:
- MIPT Supplement to R01CA55644-07S1.
P.I. David W. Scott
Agency: NIH/NCI Received 1998-2002.
Title: Regulation of B Lymphoma Growth and Apoptosis.
Major Goals: Project was to explore mechanism of B cell receptor mediated growth arrest and apoptosis in a deletional lymphoma model. Additional goals were to begin to develop Dr. Carey (then a postdoctoral fellow), along a path towards independence.
Major Findings: Acquired arsenal of techniques and began developing own, independent project. Authored and co-authored papers with David Scott group on lymphoma biology.
Total payout: $150,000.
P.I. Gregory B. Carey (Postdoc to Jr. Faculty Career Dev. Award)
Agency: NCI May 2002 - April 2007. No cost extension to April 2008.
Title: mIgM and mIgD Receptor Signaling in B-Cell Lymphoma Apoptosis Major Goals: Membrane IgM and IgD (mIgM and IgD, respectively) are differentially expressed on B cells and B cell lymphomas. BCR stimulation leads to either activation or apoptosis. The role of IgD is unknown.
Major Findings: Found that IgM stimulation suppresses PI-3K/Akt (now we also know also suppresses mTOR) axis. IgD stimulation initially suppresses PI-3K, but signal aborted. Gave first insights that IgD can actually signal. Total payout: $700,000
- Intramural Project Development Award
P.I. Gregory B. Carey
Agency: University of Maryland Aug 1, 2005-Dec 31, 2006.
Title: Role of Reactive Oxygen Species in B-Cell Receptor Mediated Death.
Major Goals: This project sought to explore if Reactive oxygen species played roles in B cell lymphoma survival and death. Results showed that do. Data used to help procure K22 and UH2 grants.
Total Payout: $15,000
Role: P.I. Gregory B. Carey (Independent Career Transition Award)
Agency: NCI 9/25/07-8/31/11*.
Title: Selective Targeting of MEK and Akt in Lymphoma and Myeloma Apoptosis.
Major Findings: K01 Project indicated role of PI-3K/Ras/Akt signaling in B lymphoma survival. BCR-suppression led to lymphoma death. Studied natural anticancer compound, Manumycin-A. Found previously unknown property - activates ROS, PP1ï¡ protein phosphatase, caspases and causes Akt and MEK deactivation and cleavage.
Total payout: ~$500,000 * = no cost extension.
- K22CA128882-03S1. (Administrative Supplement to K22CA128882. A.R.R.A.)
Role: P.I. Gregory B. Carey
Agency: NCI 10/2009 - 9/2010
Title: Selective Targeting of MEK and Akt in Lymphoma and Myeloma Apoptosis
Objectives: Salary and benefits for 2 employees plus lab supplies.
Major findings: Began understanding economy of Reactive Oxygen Species in B cell lymphoma life and death survivals. Groundwork led to UH2 award.
Total Payout: $100,000 requested and awarded.
P.I. Dr. Tonya Webb
Role: Co-P.I. Gregory B. Carey
1.2 calendar (10%)
Agency: NIH/NCI 08/1/2011 - 07/30/2013
Title: Altered Cellular Bioenergetics Influence NKT Cell Mediated Responses to Lymphoma Major Goals: This study will examine the role of HIF-1ï¡ signaling in both in vitro and in vivo models of Mantle Cell Lymphoma.
Major Findings: Finding that differences in metabolism regulate activation of NKT cells.
Award Totals: Direct: $275,000. Total: $420,750
- Carey, G.B. and Liberti, J.P. (1993) Inhibition of Tyrosine Kinase Activity Abolishes Anabolic and Lactogenic Effects of Prolactin and Growth Hormone In Nb2 Cells. Biochemistry and Molecular Biology International, 31(4): 635-642
- Carey, G.B. and Liberti, J.P. (1995) Stimulation of Receptor Associated Kinase, Tyrosine Kinase and MAP Kinase Is Required for Prolactin Mediated Macromolecular Biosynthesis and Mitogenesis in Nb2 Lymphoma. Archives of Biochemistry and Biophysics 316(1):179-189
- Grasso M., Cao, W., Lee, C., Cao, H., Zhao, Y. Joki, N., Carey, G.B. and Chang, N S. (1997) Functional Cloning of Genes Which Confer Cellular Resistance to Tumor Necrosis Factor mediated Cell Death. Guthrie Journal, Vol. 66(1): 20-24
- Carey, G.B. (1997). Prolactin Stimulates a Protein Kinase Cascade That Mediates Macromolecular Biosynthesis and Mitogenesis in Nb2 Lymphoma Cells. Guthrie Journal, Vol 66(3): 101-109
- Chang N-S., Carey G., Pratt N., Chu E. and Ou, M. (1998) Overexpression of p53 and Down regulation of Inter-ï¡ Inhibitor are Associated with Hyaluronidase Enhancement of TNF Cytotoxicity in L929 Fibroblasts. Cancer Lett. 131(1):45-54
- Carey, G.B.. and Liberti, J.P. (1998) Okadaic Acid Mimics Several Proximal Effects of Prolactin in Nb2 Lymphoma Cells. Proc Soc Exp Biol Med., 9(1):57-63.
- Carey, G.B. and Chang, N S. (1998) Cloning and Characterization of a Transforming Growth Factor Beta-1 induced Anti apoptotic Adhesion Protein TIF2. Biochem Biophys Res Commun 249(1):283-286
- Donjerkovic, D., Carey, G.B, Mueller, C., Liu, S. and Scott, D.W. (2000) Life And Death Decisions In B1 Lymphomas. In: Mechanisms In B-Cell Neoplasia: Role Of B1 And Natural Antibody Producing Cells In B-Cell Neoplasia. (ed. by M. Potter and F. Melchers) Contemp. Topics in Immunobiol 252:151-9
- Gregory B. Carey*, Dubravka Donjerkovic*, Carolyn Mueller*, Sarah Liu, Jennifer Hinshaw, Laura Tonnetti, Wendy Davidson, and David W. Scott. (2000) B-cell receptor and Fas-mediated signals for life and death. Immunological Reviews, Volume 176:105-115 (*The first three authors contributed equally to this work.)
- Nan-Shan Chang, Nicole Pratt, John Heath, Lori Schultz, Daniel Sleve, Gregory B. Carey, and Nicole Zevotek (2000) Hyaluronidase Induction of a WW Domain-Containing Oxidoreductase that Enhances Tumor Necrosis Factor Cytotoxicity. J. Biol. Chem 76(5):3361-70
- Sudeesha Kunjibettu, Sheryl Fuller-Espie, Gregory B. Carey, and Lisa M. Spain (2001) Conserved Transmembrane Tyrosine residues of the TCRï¢ Chain are Required for TCR Expression and Function in primary T cells and hybridomas. Int Immunol. 13(2):211-22
- Carey, G.B. and Scott D.W. (2001) Role of Phosphatidylinositol 3-kinase in Anti-IgM- and Anti-IgD-Induced apoptosis in B cell lymphomas. J. Immunology 163(3): 1618-26
- Gregory B. Carey, Laura Tonnetti and David W. Scott (2003). The Role of the PI3K Pathway in Anti-IgM Sensitive and Resistant B-cell Lymphomas: Failure to Disengage PI3K Pathway Signaling Confers Anti-IgM Resistance to Growth Arrest and Apoptosis in the CH12 B-Cell Lymphoma In: Molecular Mechanisms of Programmmed Cell Death. Pp 37-47. ISBN 0-306-47778-5. Edited By Yufang Shi, J. Cidlowski, D. W. Scott, and Y. B. Shi. Kluwer Academic, Plenum Publishers, New York
- Jiang-Jang Hao, Gregory B. Carey and Xi Zhan (2004) Syk-Mediated Tyrosine Phosphorylation is Required for the Association of HS1 With Lipid Rafts and BCR Signalasome Complex. J. Biol. Chem. 279 (32):33413-20
- Gregory B. Carey, Elena Semenova, Xiulan Qi, and Achsah D. Keegan (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 Research: 17(11):942-55
- Khandra T. Sears Hanako Daino and Gregory B. Carey (2008) ROS-Dependent Destruction of MEK and Akt In Manumycin Stimulated Death of Lymphoid Tumor and Myeloma Cell Lines. International Journal of Cancer 122(7):1496-505
- Yan Su, Gregory B. Carey, Maja Maric and David W. Scott (2008) B-cells Induce Tolerance by Presenting Endogenous Peptide-IgG on MHC Class II Molecules via an IFN-ï§-Inducible Lysosomal Thiol Reductase-Dependent Pathway. J Immunol, 181: 1153-1160.
- Hui Xu, Yaping Yan, Mark S. Williams, Gregory B. Carey, Jingxian Yang, Hongmei Li, Guang-Xian Zhang and Abdolmohamad Rostami (2010) MS4a4B, a CD20 Homologue in T cells, Inhibits T cell Propagation by Modulation of Cell Cycle. PLoS One. 1;5(11):e13780
- Dan Yu, Xiaoguo H. Zhan, Xianfeng Frank Zhao, Mark Williams, Gregory B. Carey, Elizabeth Smith, Yan Su, David Scott, Jianwei Zhu,Yinyin Guo, Srujana Cherukuri, Curt I. Civin, and Xi Zhan (2011) Mice Deficient In MIM Expression Are Predisposed To Tumor Formation (Oncogene Journal doi: 10.1038/onc.2011.509)
- Holly Porter, Gregory Carey and Achsah Keegan (2012) Insulin Receptor Substrate1 Expression Enhances the Sensitivity of 32D Cells to Chemotherapy- Induced Cell death Exp Cell Res. 2012 Epub. PMID: 22652453
- Yaping Yan, Guang-Xian Zhang, Mark S. Williams, Gregory B. Carey, Hongmei Li, Jingxian Yang, Abdolmohamad Rostami and Hui Xu (2012) TCR Stimulation Up-regulates MS4a4B Expression Through Induction Of AP-1 Transcription Factor During T Cell Activation. Mol Immunol. 52(2):71-8)
- Pascaline Clerc, Gregory B. Carey, Zara Mehrabian, , Michael Wei, Geoffrey D. Girnun, Stuart S. Martin, and Brian M. Polster (2012) Rapid detection of a Bcl-2-dependent ABT-737-sensitive "oprimed for death" state in cells using microplate-based respirometry . PLoS One. 12;7(8):e42487 PMID: 22880001
- Anti-MS4a4B Treatment Abrogates MS4a4B-Mediated Protection In T Cell Apoptosis and Ameliorates Experimental Autoimmune Encephalomyelitis (2013) Yaping Yan, Zichen Li1, Guang-Xian Zhang, Mark S. Williams, Gregory B. Carey, Abdolmohamad Rostami and Hui Xu. Apoptosis. 2013 Sep;18(9): 1106-19. PMID: 23801080
- Priyanka B. Subrahmanyam, Gregory B. Carey, and Tonya J. Webb (2014) Bcl-xL regulates CD1d-mediated antigen presentation to NKT cells by altering CD1d trafficking through the endocytic pathway (In review at (Journal of Immunology, 14-00155-FL)
- Sanjit Roy and Gregory B. Carey (2014) The Natural Tumoricide, Manumycin A, Induces Apoptosis by Targeting Protein Phosphatase 1ï¡ (In Review., IJC-14-0126 International Journal of Cancer)
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