Ashok Kumar
Position Title
Associate Professor
Office Phone
313-577-6213 (office)313-577-6202 (lab)
Biography
The research interests of laboratory are to study host-pathogen interactions in microbial infection caused by bacteria, viruses, and fungi. Specifically, our focus has been on developing immunomodulation strategies targeting Toll-like receptor (TLR) signaling in preventing and/or treating infectious diseases affecting the eye (e.g. keratitis and endophthalmitis) and other organs. We use cutting-edge and high throughput “omics” technologies such as transcriptomics, lipidomics, and metabolomics combined with systems biology to study host immune responses to infection. Another area of our research is to understand mechanisms of antibiotic resistance among bacteria, prevalent in hospitals and the environment and develop alternative antimicrobial therapeutics to reduce antibiotic resistance.
- Research Educator, Full time, Ph.D.
Education
- 1992 – 1995: B S. (Medical), Panjab University (DAV college), Chandigarh, India.
- 1995 –1997: M.S. (Microbiology), Kurukshetra University, Kurukshetra, Haryana, India
- 1998 – 2003: Ph. D. (Medical Microbiology), Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Faculty Appointments
- 2015 – Present Assistant Professor (Secondary), Department of Microbiology, Immunology, and Biochemistry, Wayne State University, Detroit, MI
- 2012 – Present Assistant Professor (Adjunct), Department of Biological Sciences, Oakland University, Rochester, MI
- 2010 – Present Assistant Professor (Joint), Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University, Detroit, MI
- 2010 – Present Assistant Professor (Primary), Department of Ophthalmology (Kresge Eye Institute), Wayne State University, Detroit, MI
- 2006 – 2010: Research Scientist, Kresge Eye Institute (Department of Ophthalmology), Wayne State University, Detroit, MI
Research
Research Support: NIH/NEI (R01EY019888, R01 EY026964), Research to Prevent Blindness, Astellas Pharma, Midwest Eye Banks, Fight for Sight, Alliance for Vision Research.
Research Projects:
Mechanisms regulating retinal innate immunity: The long-term goal of this project is to investigate mechanisms regulating immune responses in infectious endophthalmitis and to develop new therapeutic strategies. We are specifically interested in receptors involved in innate immunity, such as Toll-like receptors (TLRs) and Nod-like receptors (NLRs – including Nlrp3), and also signals activated. The specific role played by retinal residential (glial cells) and infiltrated (neutrophil and macrophages) cells this disease is also being investigated. Our studies demonstrated that, in addition to the inflammatory response, the activated glial cells exert antibacterial responses, including the production of antimicrobial peptides and bacterial phagocytosis, a phenomenon exhibited by classical immune cells such as neutrophils. Moreover, we showed that pretreatment with a Toll-like receptor 2(TLR2), ligand protected mice from bacterial (S. aureus) endophthalmitis.
In addition to bacteria, we also study pathogenesis of fungal infections in causing ocular infections. We recently developed, two mouse models one for Candida albicans and another Aspergillus fumigatus. In comparison to other infections, the prognosis of fungal endophthalmitis is poor due to frequent delay in diagnosis, reduced availability of therapeutic choices, and the immunocompromised status of the host. The long-term goal of this proposal is to identify genomic or metabolic alterations, which could serve as putative biomarkers for diagnosis, diseases progression, and/or therapeutic response in fungal infections and can be easily monitored in patients’ bio-fluids (aqueous, vitreous, blood, or urine).
Metabolic regulation of immune responses: Immunometabolism is an emerging area of investigation bridging distinct disciplines of microbiology, immunology, and biochemistry. It is well-established that both innate and adaptive immune cells are highly dynamic for their ability to rapidly transition from resting/patrolling to activated states in response to injury or infectious stimuli. Recent studies have revealed an important role of metabolic reprogramming, including dynamic regulation of aerobic glycolysis (the Warburg's effect), lipid synthesis and degradation, and mitochondrial activity, and the outcome of immune responses. The goal of this project is to investigate the molecular underpinnings of immunological/metabolic cross-talk in shaping immunity and to provide metabolic check points to modulate immune responses. Specifically, we are interested in elucidating the role of adenosine monophosphate (AMP)-activated protein kinase (AMPK), a master regulator of cellular metabolism.
Additionally, we are also investigating the role of specialized pro-resolving mediators (SPMs) in promoting inflammation resolution in bacterial infection. SPMs comprise omega-3 polyunsaturated fatty acid (PUFA) derived metabolites such as resolvins and protectins. Our studies revealed increased generation of both docosahexaenoic acid (DHA)-derived SPMs (RvD1, RvD5, and PD1) and their precursors (17- and 7-HDoHEs) in bacterial infection. Currently, we are investigating the interplay between inflammatory pathways activated in response to pathogen challenge and pro-resolving pathways that promotes resolution of inflammation in restoring tissue homeostasis.
Novel therapies to combat antibiotic resistance: Our research efforts in this project are geared towards understanding the mechanisms of antibiotics resistance among pathogens such as S. aureus, S. epidermidis, and A. baumannii and towards developing new and effective antimicrobials to combat these MDR bacterial strains. In our recent study (Antimicrobial Agents and Chemotherapy, 2014), we reported, for the first time, the potential use of bacteriophage endolysins to treat staphylococcal endophthalmitis in a mouse model. This project was funded by Research to Prevent Blindness (RPB) special scholar award. Currently, we are predicting and testing FDA-approved drugs for repurposing to combat antibiotic resistance.
Pathogenesis of emerging viral (Zika virus) infection: The emergence of Zika Virus (ZIKV) in both endemic and non-endemic regions around the world has been accompanied by an unprecedented expansion in the spectrum of ZIKV-associated disease pathologies. While the pathogenesis of ZIKV infection are not fully understood, we recently reported that ZIKV caused retinal lesions in mouse eyes, with the clinical presentation (i.e., chorioretinal atrophy with retinal pigment mottling) resembling features of ZIKV-associated ocular pathology in infants. Moreover, cells lining the blood-retinal barrier (BRB), including endothelial cells, were found permissive to ZIKV replication. As it is becoming increasingly clear that ZIKV infection has implications beyond microcephaly, as infants born with congenital ZIKV have pathology in their eyes, ears, limbs, and perhaps other organs. Currently, we have made multidisciplinary research teams investigating the effect of ZIKV in pregnancy, hearing disorders, neurological, and developmental problems. Given the rapid spread of ZIKV and the lack of specific treatment or vaccine, the overall goal of this project is to identify new therapeutic strategies to prevent ZIKV-associated birth defects in newborns.
Links of Interest
Selected publications
- Singh PK., Guest JM, Kanwar M, Boss J, Gao N, Juzych MS, Abrams GW, Yu Fs, and. Kumar, A. (2017) Zika virus infects cells lining the blood-retinal barrier and causes chorioretinal atrophy in mouse eyes. Journal of Clinical Investigation (JCI) Insight 2(4): e92340,
- Kumar, A., Giri, S., and Kumar, A. (2016) AICAR-mediated AMPK activation induces protective innate responses in bacterial endophthalmitis. Cellular Microbiology 18, 1815-1830
- Rajamani, D., Singh, P. K., Rottmann, B. G., Singh, N., Bhasin, M. K., and Kumar, A. (2016) Temporal retinal transcriptome and systems biology analysis identifies key pathways and hub genes in Staphylococcus aureus endophthalmitis. Scientific Reports 6, 21502.
- Singh, P. Kα., and Kumar, A. (2016) Mitochondria mediates caspase-dependent and independent retinal cell death in Staphylococcus aureus endophthalmitis. Cell Death Discovery 2, 16034
- Walia, S., Murleedharn, C., Band, J., Kanwar, Mκ., and Kumar, A. (2016) Quantitation of antibiotic resistance genes pollution in hospital waste water effluent and Urban Clinton River Water, Michigan, USA. Current Medicine Research and Practice 6, 149-151
- Talreja, D., Singh, P. K., and Kumar, A. (2015) In Vivo Role of TLR2 and MyD88 Signaling in Eliciting Innate Immune Responses in Staphylococcal Endophthalmitis. Invest Ophthalmol Vis Sci 56, 1719-1732
- Singh, P. K., Donovan, D. M., and Kumar, A. (2014) Intravitreal Injection of the Chimeric Phage Endolysin Ply187 Protects Mice from Staphylococcus aureus Endophthalmitis. Antimicrobial Agents and Chemotherapy 58, 4621-4629
- Singh, P., Shiha, M., and Kumar, A. (2014) Antibacterial responses of retinal Muller glia: production of antimicrobial peptides, oxidative burst and phagocytosis. Journal of Neuroinflammation 11, 33
- Kochan, T., Singla, A., Tosi, J., and Kumar, A. (2012) Toll-Like Receptor 2 Ligand Pretreatment Attenuates Retinal Microglial Inflammatory Response but Enhances Phagocytic Activity toward Staphylococcus aureus. Infect Immun 80, 2076-2088
- Shamsuddin, N., and Kumar, A. (2011) TLR2 mediates the innate response of retinal Muller glia to Staphylococcus aureus. Journal of Immunology 186, 7089-7097
- Kumar, A., Singh, C. N., Glybina, I. V., Mahmoud, T. H., and Yu, F.-S. X. (2010) Toll-like Receptor 2 Ligand Induced Protection against Bacterial Endophthalmitis. Journal of Infectious Diseases 201, 255-263
Patents:
https://google.com/patents/US20150335719
https://www.google.com/patents/US8889149
IN THE NEWS:
- Wayne State University scientists discover the Zika virus can damage eyes, may cause blindness
- Wayne State study finds Zika virus may cause blindness - Crains
- Link between Zika virus and blindness discovered at Wayne State