Department of Microbiology and Molecular Genetics
Department of Chemical Engineering, College of Engineering
Systems Biology of Virus-Host Networks
The Shah Lab uses viruses and engineering principles to understand how flaviviruses hijack host machinery to facilitate their own replication. We use complementary techniques of global proteomics, genetics, high-throughput sequencing to tackle this question.
Mosquito-borne flaviviruses such as dengue virus and Zika virus are a source of emerging and re-emerging infectious diseases. We study how these viruses hijack host machinery through virus-host protein interactions to better understand their replication and develop therapeutics. We have two active areas of research on flavivirus-host interactions:
Antiviral Gene Expression Program
Cells respond to viral infections by activating the expression of antiviral genes such as interferon stimulated genes (ISGs), and viruses are continually evolving ways to evade this antiviral response. We study how flaviviruses including dengue and Zika virus hijack host gene expression machinery to inhibit the antiviral innate immune response.
Autophagy is responsible for recycling cellular components into primary biological building blocks. Autophagy can be induced by the stresses elicited during pathogen infection and can be used to clear the cell of intracellular pathogens such as viruses. However, it has recently been demonstrated that several viruses, including dengue and Zika virus, benefit from certain aspects of autophagy for replication. This begs the question, how do these viruses selectively induce beneficial aspects of autophagy while not succumbing to its antiviral potential, and can we engineer controls that mimic or negate this selective induction of autophagy?
We study how flaviviruses hijack the autophagy network in a dynamic way. Specifically, we study how protein and genetic interactions in the autophagy network change during infection, and how these relate back to the viruses’ ability to replicate.
Synthetic Biology to Control Autophagy
In addition to being induced during infections, autophagy can also be induced during nutrient deprivation and high-level protein production that cells can experience in industrial settings. We use systems and synthetic biology approaches to model and engineer controls over autophagy network to improve bioreactor protein yields.
Grad Group Affiliations
- Biochemistry, Molecular, Cellular and Developmental Biology
- Integrative Genetics and Genomics
Honors and Awards
- 2014 NIAID NRSA F32 Postdoctoral Fellow
- 2010 Society of Women Engineers Graduate Scholarship
- 2007 Outstanding Graduate Student Instructor Award, UC Berkeley
- 2005 NSF IGERT Graduate Fellowship, UC Berkeley (declined)
- 2005 National Defense Science and Engineering Graduate Fellowship
- 2005 National Science Foundation Graduate Fellowship
- 2005 Roger de Friez Hunneman Prize for Outstanding Scholarship and Research, MIT
- 2004 Tau Beta Pi
- 2011 Ph.D. Chemical Engineering University of California, Berkeley
- 2005 B.Sc. Chemical Engineering Massachusetts Institute of Technology
De Maio FA, Risso G, Iglesias NG, Shah P, Pozzi B, Gebhard LG, Mammi P, Mancini E, Yanovsky MJ, Andino R, Krogan N, Srebrow A, Gamarnik AV. (2016) The Dengue Virus NS5 Protein Intrudes in the Cellular Spliceosome and Modulates Splicing. PLoS Pathogens 12(8):e1005841.
Heaton NS, Moshkina N, Fenouil R, Gardner TJ, Aguirre S, Shah PS, Zhao N, Manganaro L, Hultquist JF, Noel J, Sachs D, Sachs DH, Hamilton J, Leon PE, Chawdury A, Tripathi S, Melegari C, Campisi L, Hai R, Metreveli G, Gamarnik AV, García-Sastre A, Greenbaum B, Simon V, Fernandez-Sesma A, Krogan NJ, Mulder LC, van Bakel H, Tortorella D, Taunton J, Palese P, Marazzi I. (2016) Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection. Immunity 44(1):46-58.
Shah PS, Wojcechowskyj JA, Eckhardt M, Krogan NJ. (2015) Comparative mapping of host-pathogen protein-protein interactions. Current Opinion in Microbiology 27:62-8.
Ramage HR, Kumar GR, Verschueren E, Johnson JR, Von Dollen J, Johnson T, Newton B, Shah P, Horner J, Krogan NJ, Ott M. (2015) A combined proteomics/genomics approach links hepatitis C virus infection with nonsense-mediated mRNA decay. Molecular Cell 57(2):329-40.
Miller-Jensen K, Skupsky R, Shah PS, Arkin AP, Schaffer DV. (2013) Genetic selection for context-dependent stochastic phenotypes: Sp1 and TATA mutations increase phenotypic noise in HIV-1 gene expression. PLoS Computational Biology 9(7):e1003135.
Shah PS, Pham NP, Schaffer DV. (2012) HIV develops indirect cross-resistance to combinatorial RNAi targeting two distinct and spatially distant sites. Molecular Therapy : The Journal of the American Society of Gene Therapy 20(4):840-8.
Ashton RS, Conway A, Pangarkar C, Bergen J, Lim KI, Shah P, Bissell M, Schaffer DV. (2012) Astrocytes regulate adult hippocampal neurogenesis through ephrin-B signaling. Nature Neuroscience 15(10):1399-406.
Burnett JC, Miller-Jensen K, Shah PS, Arkin AP, Schaffer DV. (2009) Control of stochastic gene expression by host factors at the HIV promoter. PLoS Pathogens 5(1):e1000260.
Leonard JN, Shah PS, Burnett JC, Schaffer DV. (2008) HIV evades RNA interference directed at TAR by an indirect compensatory mechanism. Cell Host & Microbe 4(5):484-94.
Brault PA, Kariapper MS, Pham CV, Flowers RA, Gunning WT, Shah P, Funk MO. () Protein micelles from lipoxygenase 3. Biomacromolecules 3(4):649-54.
Vahedi-Faridi A, Brault PA, Shah P, Kim YW, Dunham WR, Funk MO. (2004) Interaction between non-heme iron of lipoxygenases and cumene hydroperoxide: basis for enzyme activation, inactivation, and inhibition. Journal of the American Chemical Society 126(7):2006-15.