Michaela Gack, Assistant Professor of Microbiology and ImmunobiologyJul 14th, 2013 | By Laura Liu | Category: Faculty profiles, G1, G2
Research Interests: Understanding the molecular mechanisms of how cells detect viral infections and induce signaling cascades that activate the innate immune response, and conversely, how viruses antagonize this response and evade the immune system.
Dr. Michaela Gack’s research focuses on virus-host interactions, specifically on innate immune sensing of RNA viruses by cytosolic receptors and the interferon-mediated antiviral defense that then ensues. Her laboratory has three main research areas: (1) how two cytosolic receptors, RIG-I (retinoic acid-inducible gene-I) and MDA5 (melanoma differentiation-associated gene 5), sense viral RNA and how they themselves are tightly regulated to induce an antiviral type-I interferon response. Recently, Gack and colleagues identified two essential activators of the cytosolic sensors RIG-I and MDA5: the ubiquitin E3 ligase TRIM25 which ubiquitinates RIG-I to induce interferon gene expression, and more recently – the phosphatase PP1 which dephosphorylates both RIG-I and MDA5, thereby leading to innate immune signaling. (2) Understanding viral inhibition of the interferon response is also essential to preventing viral pathogenesis, and Gack has shown that a protein from human, avian, and swine influenza viruses can inhibit TRIM25 and obliterate the cellular interferon response. This finding highlights the importance of TRIM molecules, a protein family with more than 80 members in humans, and is the focus of the third research area in the lab: (3) to identify the role of different TRIM proteins in antiviral defense mechanisms.
Gack and colleagues are using a multi-pronged approach to realize their goals, with expertise in biochemistry, molecular biology, proteomics, and cellular biology. Furthermore, the ubiquitous nature of the proteins of interest allows them to use many model systems for their studies, and their impressive viral repertoire includes influenza virus, dengue virus, measles virus, herpes simplex virus, and several tumor viruses including the Kaposi’s sarcoma-associated herpesvirus (KSHV).
Currently, the lab is comprised of 2 postdoctoral fellows, 4 graduate students (from 3 different Ph.D. programs), and 2 research assistants
- Undergraduate: Dr. Gack received a Master’s Degree in Molecular Medicine from the Friedrich-Alexander University (FAU) in Erlangen-Nuremberg, Germany. The program allowed her to interact with medical students, taking the same courses such as anatomy, physiology and genetics. Her master’s research was focused on oncogenic gamma-herpesviruses and how virus-encoded oncogenes modulate cell signaling processes.
- Ph.D.: Graduated in 2008 in Molecular Virology from the joint graduate training program (“Viruses of the Immune System”) between Harvard Medical School and FAU Erlangen-Nuremberg, where she studied in the laboratory of Dr. Jae Jung and discovered the vital interaction between RIG-I and TRIM25 for eliciting an effective antiviral response.
- Postdoctoral Fellowship at the University of Southern California (2008-2009); focus of research: immune escape of influenza A viruses.
- Gack was recruited back to Harvard in 2009 and hired as an Instructor at the New England Primate Center before being appointed as an Assistant Professor in the Department of Microbiology and Immunobiology in February 2011. Her laboratory is now located at the New Research Building of the HMS Quad.
The Path to Research
Though she was always interested in science, Gack reached a crossroads in her early career: science or medicine? After completing the Molecular Medicine master’s program, Gack had her answer: she realized that she had fallen in love with medical research and lab work. The program gave her exposure to many different fields, including physiology and genetics, but it was her internship in virology and research on oncogenic herpesviruses that captured her interests. How these viruses were able to induce cancer, control and manipulate cells using viral oncogenes that took millions of years to acquire were all questions that drove Gack to pursue a Ph.D. and career in virology.
- Favorite Book: Travel guides and other books about different countries to learn more about their cultures, architecture and foods.
- Favorite Movie: independent, foreign movies with a different perspective
- Favorite Vacation Spot: Italy, Rome
- Favorite Restaurant: Fugakyu in Brookline (Japanese); for unique foods, Ariana in Allston (Afghan Cuisine)
- Favorite thing to do in Boston: Exploring Boston including the museum culture, and walking around the Esplanade and Deer Island in Boston Harbor.
Advice for Graduate Students
“Do what you love. If you love what you do and are happy, you will be more likely to succeed as well. My second advice is to choose good role models, to learn how they think and do science and practically approach problems.”