Nahid F. Mivechi, PhD
Professor, Radiation Oncology
Director, Radiobiology Program
Molecular Chaperone Biology Research Group
Dr. Nahid Mivechi has a long-standing interest in understanding the signaling pathways that govern cellular responses to disruption in protein homeostasis under physiological or pathological processes, including cancer and neurodegenerative diseases. She has extensive experience in molecular and cancer biology and has demonstrated a record of success in the research areas of regulation and function of heat shock transcription factors (HSFs) and heat shock protein (HSPs) in disease conditions.
For this research, she has developed several animal models including conventional and conditional HSF or HSP-knockout mouse lines. Her strongest contribution is in dissecting cellular and molecular mechanisms regulated by HSFs and molecular chaperone machines for cancer (Breast, T-ALL, AML, Liver), neurodegeneration (Alzheimer’s disease, TBI, Parkinson’s disease and Zebrafish neurodevelopment) and metabolic diseases. A specific focus of her research program encompasses the study of the protective adaptive response of organisms to cellular and exogenous stress, which involves the activation of HSF1. Her long-standing research has established the essential function of HSF1 in hepatocellular carcinoma (HCC) development by regulating whole body metabolism (glucose utilization, gluconeogenesis, lipogenesis and cellular bioenergetics) as well as components of metabolic syndrome (insulin sensitivity and obesity). Ongoing research is devoted to study the therapeutic effects of targeting Hsf1 on HCC and establishing a possible causal relationship between Hsf1-driven alterations in hepatic or total body metabolism (obesity) and HCC development. The recent discovery in the laboratory that the broad spectrum of activities of Hsf1 in providing heterotypic support for the tumor may also include its ability to interfere with robust anti-tumor immunity development supports a potentially paradigm-shifting research to improve adaptive tumor immunity by targeting Hsf1 activity. A major goal of her research is to extend these striking findings and test novel hypotheses regarding the underlying mechanisms, so that we can fully explore the prognostic and therapeutic value of metabolic alterations caused by Hsf1 inactivation in liver cancer.
The Nahid Mivechi Lab
Health Sciences Campus
1410 Laney Walker Blvd., CN-3153, Augusta, GA 30912
He, B. Meng, Y-H., Mivechi, N. F. GSK-3 and ERK MAP kinase inactivate heat shock transcription factor-1 by facilitating the disappearance of transcriptionally-active granules after heat shock. Mol. Cell. Biol. 18:6624-6633, 1998.
Zhang, Y., Serinagesh, K., Dai, R, Mivechi, N. F. Structural Organization and promoter analysis of murine heat shock transcription factor-1 gene. J. Biol. Chem., 273:32514-32521, 1998.
Dai, R. Frejtag, W., He, B., Zhang, Y. Mivechi, N.F. JNK targeting and phosphorylation of heat shock factor-1 suppress its transcriptional activity. J. of Biol. Chem, 275:18210-18218, 2000.
Huang, L., Mivechi, N.F., Moskofidis, D. Insights into regulation and function of the major stress-induced hsp 70 molecular chaperone in vivo: analysis of mice with targeted gene disruption of hsp70.1 or 70.3 genes. Mol. Cell. Biol. 21:8571-8591, 2001.
Zhang, Y., Huang, L., Zhang. J., Moskofidis, D., Mivechi, N.F. Targeted disruption of hsf1 leads to lack of thermotolerance and defines tissue-specific regulation for stress-inducible Hsp molecular chaperones. J. Cell. Biochem., 86:376-393, 2002.
Homma, S., Jin, X., Wang, G., Tu, T., Min, J-N., Yanasak, N., Mivechi, N. F. Demyelination, astrogliosis, and accumulation of ubiquitinated proteins, hallmarks of CNS disease in hsf1-deficient mice. Journal of Neuroscience 27:7974-7986, 2007.
Binnur Eroglu, Demetrius Moskophidis, and Nahid F. Mivechi (2010). Loss of heat shock protein (Hsp) 110 leads to tau hyperphosphorylation and early accumulation of insoluble amyloid-b peptide in mouse model of Alzheimer’s disease. Molecular Cell Biology, 19: 4623-4643.
Xiongjie Jin, Demetrius Moskophidis, and Nahid F. Mivechi (2011). Hsf1 is a key of determinant of HCC development by regulating hepatic steotosis and metabolic syndrome. Cell Metabolism, 14: 91-103. PMID: 21723507.
Xi C, Y., Hu, P. Buckhaults, D. Moskophidis, and N.F. Mivechi (2012). Heat shock factor Hsf1 cooperates with ErbB2 (Her2/Neu) protein to promote mammary tumorigenesis and metastasis. J Biol. Chem. 287:35646-35657. PMCID: 22847003.
Eroglu, E., Kimbler, D. E., Pang, J., Choi, J., Moskophidis, D., Yanasak, N., Dhandapani, K.M., Mivechi, N.F. (2014) Therapeutic inducers of the HSP70/HSP110 protect mice against traumatic brain injury. J Neurochem. 2014 Sep;130(5):626-41. Epub 2014 Jul 4.PMID: 24903326.
Eroglu, B., Min, J-N., Zhang, Y., Eroglu, A., Mivechi, N.F. (2014). An essential role for heat shock transcription factor binding protein 1 (HSBP1) during early embryonic development. Developmental Biology, 386: 448-460. PMID: 24380799.
Qiao, A., Jin, X., D. Moskophidis and N.F. Mivechi. (2017). The transcriptional regulator of the chaperone response HSF1 controls hepatic bioenergetics and protein homeostasis. Journal of Cell Biology, 216: 723-741.
Xiongjie Jin, Aijun Qiao, Demetrius Moskophidis, and Nahid Mivechi. (2018). Modulation of Heat Shock Factor 1 Activity through Silencing of Ser303/Ser307 Phosphorylation Supports a Metabolic Program Leading to Age-Related Obesity and Insulin Resistance. Mol. Cell. Biology, August 28, 38: 1-26, PMID: 29941492.
Cho, W-K., X. Jin, Pang, J., Wang, Y., N.F. Mivechi*, and D. Moskophidis* (2019). The Molecular Chaperone Heat Shock Protein 70 Controls Liver Cancer Initiation and Progression by Regulating Adaptive DNA Damage and Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Signaling Pathways. Mol. Cell. Biology, 39:1-33.
Binnur Eroglu, Junfeng Pang, Xiongjie Jin, Caixia Xi, Demetrius Moskophidis, Nahid F. Mivechi (2020). HSF1-mediated Control of Cellular Energy Metabolism and mTORC1 Activation Drive Acute T Cell Lymphoblastic Leukemia Progression. Molecular Cancer Research, Nov.19. 18:463-476.