Dr. Hakami obtained his Ph.D. in Biochemistry in the laboratory of the Nobel Laureate Professor Har Gobind Khorana, at the Massachusetts Institute of Technology. He was then awarded a NRSA fellowship from NIH and completed postdoctoral training at Harvard Medical School (HMS) and subsequently at the National Human Genome Research Institute. He joined the faculty at George Mason University in 2011.
Infectious Diseases, Host Response Mechanisms in Infectious Diseases, and Development of Novel Therapeutics and Vaccines
New therapeutics and vaccines are urgently needed to combat a number of emerging and reemerging infectious diseases, especially in light of the appearance of drug resistant strains. A sobering reminder of this urgency is the findings by the World Health Organization that infectious diseases are major causes of death, disability, and social and economic disruptions for millions of people worldwide. In addition, concerns over the use of highly infectious pathogens for bioterrorism have risen dramatically over the past few years, especially given the limitations in efficacy of many current vaccines and therapeutics. Some agents of great concern include the bacterial pathogens Yersinia pestis and Bacillus anthracis, and the viral pathogen Rift Valley fever virus (RVFV). The main focus of Hakami’s laboratory is the discovery of critical host responses to infection caused by these pathogens and functional characterization of the identified pathways. The ultimate goal is to apply our molecular understanding of the host-pathogen interactions towards developing novel and effective therapeutics and vaccines. One central approach is to understand the signaling changes during infection through the application of proteomic and phosphoproteomic tools and performing detailed in vitro and in vivo functional analysis to discover their significance during pathogenesis. For instance, phosphoproteomic and functional studies performed by Dr. Hakami and colleagues has demonstrated that the serine/threonine kinase AKT becomes hyperactivated during Y. pestis infection and leads to a suppression of apoptosis and increased survival of infected cells during the early phase of infection. In a separate collaborative study, through proteomic analysis of highly purified RVFV virions and functional tests the laboratory has demonstrated a role for heat shock proteins in mediation of RVFV infection.
Another central focus of host response studies in Hakami laboratory is to understand the critical cell-cell communication mechanisms that may be mediated through exosomes released from infected cells. Exosomes are small host vesicles that typically are released as a result of cell activation and carry a complement of proteins and genetic materials, including mRNA and miRNA. Recent evidence has demonstrated that exosomes can have either activation or inhibitory effect s on their recipient immune cells, such as direct or indirect antigen presentation and antigen transfer, or T cell killing and inhibition of differentiation. Using their B. anthracis and Y. pestis infection models, the Hakami laboratory has demonstrated a change in the levels of released exosomes subsequent to infection. They are currently assaying the functional relevance of purified exosome preparations and identifying the miRNA and protein complements of exosomes that may be tied to the mechanisms of pathogenesis.
- Alem, K. Yao, D. Lane, V. Calvert, E. F. Petricoin, L. Kramer, M. L. Hale, S. Bavari, R. G. Panchal, and R. M. Hakami* (2015). Host response during Yersinia pestis infection of human bronchial epithelial cells involves negative regulation of autophagy and suggests a modulation of survival-related and cellular growth pathways. Front Microbiol. 2015 Feb 13;6:50. doi: 10.3389/fmicb.2015.00050.
- Fleming, G. Sampey, M.-C. Chung, C. Bailey, M. van Hoek, F. Kashanchi, and R. M. Hakami* (2014). The Carrying Pigeons of the Cell: Exosomes and their Role in Diseases Caused by Human Pathogens. Pathogens and Disease, doi: 10.1111/2049-632X.12135. [Epub ahead of print]
- E. Nuss, K. Kehn-Hall, A. Benedict, J. Costantino, M. Ward, B. D. Peyser, L. E. Tressler, L. M. Wanner, H. F. McGovern, A. Zaidi, S. Anthony, K. P. Kota, S. Bavari, and R. M. Hakami* (2014). Multi-Faceted Proteomic Characterization of Rift Valley Fever Virus Virions and Identification of Specific Heat Shock Proteins, Including HSP90, as Important Viral Host Factors. PloS ONE, May 8;9(5):e93483. doi: 10.1371/journal.pone.0093483
- Sampey, S. Meyering, M. Zadeh, M. Saifuddin, R. M. Hakami*, and Fatah Kashanchi* (2014). Exosomes and their role in CNS viral infections. J. Neurovirol., Feb 28. PMID: 24578033 [Epub ahead of print]
* Co-Corresponding Author
- Narayanan, M. Amaya, K. Voss, M. Chung, A. Benedict, G. Sampey, K. Kehn-Hall, A. Luchini, L. Liotta, C. Bailey, A. Kumar, S. Bavari, R. M. Hakami, F. Kashanchi (2014). Reactive Oxygen Species Activate NFκB (p65) and p53 and Induce Apoptosis in RVFV Infected Liver Cells. Virology, 449, 270–286
- H. Tonry, S. G. Popov, A. Narayanan, F. Kashanchi, R. M. Hakami, C. Carpenter, C. Bailey, and M.-C. Chung (2013). In vivo Murine and In vitro M-cell Models of Gastrointestinal Anthrax. Microbes and Infection,15(1), 37-441.
- Narayanan, S. Iodranskiy, R. Das, R. Van Duyne, S. Santos, E. Jaworski, I. Guendel, G. Sampey, E. Gerhardt, M. Iglesias-Ussel, R. M. Hakami, K. Kehn-Hall, M. Young, C. Subra, C. Gilbert, C. Bailey, F. Romerio, F. Kashanchi (2013). Exosomes Derived from HIV-1-Infected Cells Contain Trans-activation Response Element RNA. J Biol. Chem., 288(27), 20014-33.