Ashok K. Shetty, PhD

Education and Training

• All India Institute of Medical Sciences, (New Delhi, India), PhD in Neuroscience, 1990
• University of Mysore - (Mysore, India) , M.Sc. in Human Anatomy, 1983
• University of Mysore - (Mysore, India), B.Sc. in Zoology, chemistry, Botany , 1980

Research Interests

• Dr. Ashok K. Shetty's laboratory is dedicated to developing innovative therapies for conditions such as Alzheimer's Disease, Traumatic Brain Injury, and Gulf War Illness.
• Alzheimer's disease (AD) affects 7 million Americans and 60 million worldwide, causing severe consequences for both patients and their families. Currently, there is no effective therapy available for treating AD. Dr. Shetty's laboratory is developing an innovative nasal spray composed of human neural stem cell-derived extracellular vesicles. These tiny vesicles contain potent antiinflammatory and neuroprotective molecules which can curb the overactivity of brain-resident immune cells called microglia and the neuronal function supportive astrocytes to reduce chronic neuroinflammation, amyloid plaques, and neurofibrillary tangles in the brain. Using animal models of AD, this approach has been found to slow down the progression of cognitive decline and the associated neuropathological changes for extended periods, with therapeutic interventions at the early stages of the disease. Ongoing National Institutes of Health-funded studies are exploring the feasibility of reversing or alleviating cognitive decline in old age and in the middle and advanced stages of AD using human neural stem cell-derived extracellular vesicles or engineered extracellular vesicles from various stem/progenitor cells.
• Traumatic brain injury (TBI) affects both military and civilian populations, causing devastating effects on long-term brain function and creating a considerable burden on the U.S. healthcare system. Over 5 million Americans are living with a disability resulting from TBI, with treatment costs of 30 billion dollars per year. Dr. Shetty's laboratory is investigating the therapeutic efficacy of extracellular vesicles from human bone marrow-derived mesenchymal stem cells and human pluripotent stem cell-derived neural stem cells in models of TBI. Stem cell-derived nanosized vesicles are naturally enriched with multiple therapeutic molecules capable of mediating antiinflammatory and neuroprotective effects and triggering the production of new neurons. When intranasally administered early (60-90 minutes) after brain injury, these vesicles are proficient in reducing brain tissue loss, blocking the progression of acute neuroinflammation into chronic neuroinflammation, and maintaining better cognitive and mood function. Ongoing studies funded by the National Institutes of Health and Department of Defense are exploring the potential of naive and engineered stem cell-derived extracellular vesicles to reverse or alleviate brain dysfunction with intranasal interventions at extended periods after different types of brain injury, including penetrating brain injury and repeated closed head injury (repeated mild concussions).
• Gulf War Illness (GWI) affects nearly 40% of 700,000 veterans who served in the first Gulf War, which is characterized by persistent cognitive and mood impairments. Dr. Shetty's laboratory has been investigating the mechanisms underlying persistent mild cognitive and memory impairments in veterans with Gulf War Illness using animal models. Such studies have identified several therapeutic targets and compounds/drugs capable of improving brain function. One of these discoveries has progressed to clinical trials in veterans with Gulf War Illness, which is currently being conducted in collaboration with a clinician at the Baylor College of Medicine. In this trial, Dr. Shetty's team tracks changes in brain inflammation in patients receiving treatment by analyzing microglia and astrocyte-derived extracellular vesicles found in their blood, employing a liquid biopsy approach. Ongoing studies funded by the Department of Defense are assessing the possible accelerated cellular senescence and aging and microglial abnormalities in Veterans with Gulf War illness and testing the efficacy of a senolytic fisetin and a psychedelic compound Psilocybin to improve brain function in animal models of Gulf War Illness.
• In summary, Dr. Shetty’s research program is focused on gaining insights into mechanisms underlying brain dysfunction and developing novel strategies for devastating conditions such as Alzheimer's disease, Traumatic Brain Injury, and Gulf War Illness.

Awards, Recognition and Service

• Honoree of Fast Company's World Changing Ideas-2-25
• Texas A&M University Distinguished Professor Award- 2024
• AAAS Fellow conferred by American Association For The Advancement of Science - (Washington D.C., District of Columbia, United States)
• Research Career Scientist Award conferred by United States Department of Veterans Affairs - (Washington D.C., District of Columbia, United States)

Representative Publications

1) Rao S, Madhu LN, Babu RS, Shankar G, Kotian S, Nagarajan A, Upadhya R, Narvekar E, Cai JJ, Shetty AK. Extracellular vesicles from hiPSC-derived NSCs protect human neurons against Aβ-42 oligomers induced neurodegeneration, mitochondrial dysfunction and tau phosphorylation. Stem Cell Research & Therapy, 18;16(1):191, 2025.

2) Kodali M, Madhu LN, Somayaji Y, Attaluri S, Huard C, Panda PK, Shankar G, Rao S, Shuai B, Gonzalez JJ, Oake C, Hering C, Babu RS, Kotian S, Shetty AK. Residual microglia following short-term PLX5622 treatment in 5xFAD mice exhibit diminished NLRP3 inflammasome and mTOR signaling, and enhanced autophagy. Aging Cell, 24(2): e14398, 2025.

3) Madhu LN, Kodali M, Upadhya R, Rao S, Somayaji Y, Attaluri S, Shuai B, Kirmani M, Gupta S, Maness N, Rao X, Cai JJ, Shetty AK: Extracellular vesicles from human-induced pluripotent stem cell-derived neural stem cells alleviate proinflammatory cascades within disease-associated microglia in Alzheimer's disease. Journal of Extracellular Vesicles, 13: e12519, 2024.

4) Kodali M, Madhu LN, Kolla VSV, Attaluri S, Huard C, Somayaji Y, Shuai B, Jordan C, Rao X, Shetty S, Shetty AK. FDA-approved cannabidiol [Epidiolex^®] alleviates Gulf War Illness-linked cognitive and mood dysfunction, hyperalgesia, neuroinflammatory signaling, and declined neurogenesis. Military Medical Research, 11(1): 61, 2024.

5) Kodali M, Madhu LN, Reger RL, Milutinovic B, Upadhya R, Gonzalez JJ, Attaluri S, Shuai B, Gitai DLG, Rao S, Choi JM, Jung SY, Shetty AK: Intranasally administered human MSC-derived extracellular vesicles inhibit NLRP3-p38/MAPK signaling after TBI and prevent chronic brain dysfunction. Brain Behav Immun. 108:118-134, 2023.

6) Ayyubova G, Kodali M, Upadhya R, Madhu LN, Attaluri S, Somayaji Y, Shuai B, Rao S, Shankar G, Shetty AK. Extracellular vesicles from hiPSC-NSCs can prevent peripheral inflammation-induced cognitive dysfunction with inflammasome inhibition and improved neurogenesis in the hippocampus. Journal of Neuroinflammation, 20:297, 2023.

7) Zanirati G, Shetty PA, Shetty AK. Neural stem cells persist to generate new neurons in the hippocampus of adult and aged human brain - Fiction or accurate? Ageing Research Reviews, 92:102133, 2023.

8) Upadhya D, Attaluri S, Liu Y, Hattiangady B, Castro OW, Shuai B, Dong Y, Zhang SC, Shetty 5K. Grafted hPSC-derived GABA-ergic interneurons regulate seizures and specific cognitive function in temporal lobe epilepsy. NPJ Regenerative Medicine, 7(1):38, 2022.

9) Madhu LN, Kodali, M, Attaluri S, Shuai B, Melissari L, Rao X, Shetty AK. Melatonin improves brain function in a model of chronic Gulf War Illness with modulation of oxidative stress, NLRP3 inflammasomes, and BDNF-ERK-CREB pathway in the hippocampus. Redox Biology, 43:101973, 2021.

10) Wei Z-YD, Shetty AK. Treating Parkinson’s disease by astrocyte reprogramming: Progress and challenges. Science Advances, 7(26): eabg3198, 2021.

11) Upadhya R, Madhu LN, Attaluri S, Gitai DLG, Pinson MR, Kodali M, Shetty G, Zanirati G, Kumar S, Shuai B, Weintraub ST, Shetty AK: Extracellular vesicles from human iPSC-derived neural stem cells: miRNA and protein signatures, and antiinflammatory and neurogenic properties. Journal of Extracellular Vesicles, 9: 1809064, 2020.

12) Upadhya D, Hattiangady B, Castro O, Shuai B, Kodali M, Attaluri S, Bates A, Dong Y, Zhang S-C, Prockop DJ, Shetty AK (2019): Human iPSC-derived MGE cell grafting after status epilepticus attenuates chronic epilepsy and co-morbidities via synaptic integration. Proc Natl Acad Sci USA. 116(1):287-296, 2019.

13) Kodali M, Hattiangady B, Shetty G, Bates A, Shuai B, Shetty AK (2018): Curcumin Treatment Leads to Better Cognitive and Mood Function in a Model of Gulf War Illness with Enhanced Neurogenesis, and Alleviation of Inflammation and Mitochondrial Dysfunction in the Hippocampus. Brain, Behavior and Immunity. 69:499-514, 2018.

14) Long Q, Upadhya D, Hattiangady B, Kim DK, An SY, Shuai B, Prockop DJ, Shetty AK: Intranasal MSC-derived A1-exosomes ease inflammation and prevent abnormal neurogenesis and memory dysfunction after status epilepticus. Proc Natl Acad Sci USA, 114(17): E3536-E3545, 2017.

Grant Information

Extramural Grant Support

Current Grants

Department of Defense Grant, HT94252510299, Shetty AK (PI), Intranasal Human Neural Stem Cell-Derived EVs for Repeated Closed Head Injury, 09/30/2025 - 09/29/2029.

Department of Defense Grant, HT94252510566, Shetty AK (PI), Psilocybin Therapy for Enhancing Brain Function in Gulf War Illness, 07/01/2025 - 06/30/2028.

National Institute on Aging (NIH-NIA) Grant, 1R01 AG075440-01, Shetty AK (PI), Neural Stem Cell-derived EVs for Improving Aged Brain Function, 08/01/2022 - 04/30/2027.

National Institute on Aging (NIH-NIA) Grant, 1RF1AG074256-01A1, Shetty AK (PI), Intranasal Treatment of Stem Cell-derived Extracellular Vesicles for Alzheimer's Disease. 08/01/2022 - 07/31/2027.

Department of Defense Grant, W81XWH-22-1-0413, Shetty AK (Sub-contract PI), Clinical Evaluation of Montelukast on Cognitive and Mood Dysfunction and Neuroinflammation in Veterans with Gulf War Illness (Parent Grant PI: Helmer D, Baylor College of Medicine), 09/01/2025 - 08/31/2027.

Department of Defense Grant, HT94252310972, Shetty AK (PI), Contribution of Cellular Senescence and Brain Aging to Cognitive Dysfunction in Gulf War Illness. 09/30/2023 - 09/29/2026.

Department of Defense Grant, W81XWH2210565, Shetty (PI), Probing Neuroinflammation in GWI via Studies on Gulf War Veteran-derived Microglia, 09/30/2022 - 09/29/2026.

Steadman Philippon Research Institute Grant, Shetty AK (PI), Psilocybin and Cannabidiol for Alleviating Brain Dysfunction Following Chronic Stress, 12/01/2024 - 11/30/2025.

Department of Defense Grant, W81XWH-20-1-0568, Shetty AK (PI), Tracking Neuroinflammation in GWI from Brain-Derived Extracellular Vesicles in the Blood, 09/01/2020 - 08/31/2025.

Pending Grants

National Institute for Neurological Disorders and Stroke (NIH-NINDS) Grant 2R01 NS106907-06, Shetty AK (PI), Mesenchymal Stem Cell Derived Extracellular Vesicles for Traumatic Brain Injury, 07/1/2025 - 06/30/2030.

Department of Defense Grant, Shetty AK (Sub-contract PI), Brain SHIELD: A Field-Deployable Hydrogel Drug Delivery System for Localized Treatment of TBI (Parent grant PI: Dr. Melissa Wright, Luna Labs), 11/01/2025-10/31/2027.