Hilary Grosso Jasutkar, MD, PhD

Hilary Grosso Jasutkar, MD, PhD earned her PhD in neuroscience in 2012 under the supervision of Dr. M. Maral Mouradian, and her medical degree in 2014, both at Robert Wood Johnson Medical School. She then completed a medical internship at Lankenau Medical Center, followed by a residency in neurology at Columbia University Irving Medical Center (CUIMC). After her residency training, Dr. Grosso pursued a medical fellowship in the management of age-related disorders of cognition in the CUIMC Neurology Department’s Division of Aging and Dementia, during which time she worked as a post-doctoral fellow in the laboratory of Dr. Ai Yamamoto at CUIMC. She then joined the Robert Wood Johnson Medical School Institute for Neurological Therapeutics as a clinical and research Instructor in Neurology in 2021. 

Dr. Grosso’s research focuses on understanding the molecular mechanisms by which autophagy supports synaptic function, and how protein misfolding in neurodegenerative diseases disrupts synaptic autophagy. Currently she is using genetically modified mice to model autophagy loss in the adult, and to study the impact of the Alzheimer’s disease-associated protein APP on autophagy at the synapse. 

About

Our long-term goals are to identify steps in this pathway that could be targets for the development of disease-modifying therapies for neurodegenerative conditions.

We utilize genetically modified mouse models and primary cell cultures derived from these animals to investigate the role of autophagy in both normal brain aging and disease, as well as how Alzheimer’s disease-associated pathophysiology disrupts autophagy. Our methods include behavioral, biochemical, immunohistochemical, and cell biological investigations of our model systems.

The Grosso Lab was established in August 2021, as a core member of the Robert Wood Johnson Medical School Institute for Neurological Therapeutics, located on the Piscataway Campus of Rutgers Health.

Research
 

Autophagy in Synaptic Homeostasis and Cognition

Autophagy is a critical homeostatic pathway within the cell, yet when we deactivate it in adult mice, there is a not a catastrophic failure of cellular function. Rather, compensatory mechanisms kick in and the animals continue to function relatively normally. However, we have found that the synapse is uniquely reliant upon autophagy for synaptic protein homeostasis. In parallel, we identified a time-dependent decline in cognitive function after autophagy deactivation. The goal of this project is to establish a causative link between the loss of synaptic protein homeostasis and impaired cognitive function in the absence of functional autophagy.

Autophagy in Normal Cognitive Aging

Normal aging is associated with a decline in cognitive function, which is referred to as “normal cognitive aging.” Autophagic function also declines with age, yet its importance to the synapse rises over the lifespan. The goal of this project is to determine how autophagic processing of synaptic proteins changes with age, and whether enhancing autophagic clearance of synaptic cargo can protect against this normal cognitive aging. *This work is funded in part by The Glenn Foundation for Medical Research and AFAR Grant for Junior Faculty.

The Impact of Alzheimer's Disease Associated Pathology on Autophagic Function

Autophagy has long been implicated in the pathophysiology of Alzheimer's disease, but many questions remain unanswered regarding when during the disease process autophagy becomes disrupted, how Alzheimer’s disease pathophysiology impacts autophagic function, and how, in turn, disruption of autophagy contributes to further degeneration. This project utilizes a mouse model of Alzheimer’s disease and cell cultures derived from that model organism to investigate these questions. *This work funded in part by The Busch Biomedical Research Grant. 

Region-specific reliance upon autophagy 

One particularly enigmatic aspect of neurodegenerative diseases is the early regional vulnerability. We have found differences in how various brain regions utilize autophagy. The goal of this project is to better characterize these regional differences and to investigate if the differential reliance on autophagy may contribute to the regional vulnerability seen in neurodegenerative diseases.

The Mechanistic Role of Autophagy in Synapses

Disruption of autophagy interferes with synaptic function, and synaptic activity upregulates autophagic activity. Therefore, it has often been assumed that autophagy actively participates in the response of the synapse to a signal, for example, by participating in synaptic vesicle (SV) release in response to an action potential or removing neurotransmitter receptors from the post-synaptic membrane in response to signals to decrease synaptic strength. However, autophagy also has basal activity in synapses, suggesting that it is necessary for synapse homeostasis as well. Disruption of this function could alone be sufficient to explain the synaptic alterations that follow autophagy impairment. The goal of this project is to use live-cell imaging of autophagy deactivated cells to differentiate between these possibilities.

Publications
 

Selected Publications:

1. Grosso Jasutkar, H. and A. Yamamoto, Autophagy at the synapse, an early site of dysfunction in neurodegeneration. Current Opinion in Physiology, 2023. 32: p. 100631.

2. Yang, Y.J., et al., The tissue-specific autophagic response to nutrient deprivation. bioRxiv, 2022: p. 2022.11.12.516287.

3. Grosso Jasutkar, H., S.E. Oh, and M.M. Mouradian, Therapeutics in the Pipeline Targeting α-Synuclein for Parkinson's Disease. Pharmacological Reviews, 2022. 74(1): p. 207-237.

4. Grosso Jasutkar, H. and A. Yamamoto, Do Changes in Synaptic Autophagy Underlie the Cognitive Impairments in Huntington's Disease? Journal of Huntington's disease, 2021. 10(2): p. 227-238.

5. Zhang, J., H.G. Jasutkar, and M.M. Mouradian, Targeting transglutaminase 2 as a potential disease modifying therapeutic strategy for synucleinopathies. Neural Regen Res, 2021. 16(8): p. 1560-1561.

6. Zhang, J., et al., Transglutaminase 2 Depletion Attenuates α-Synuclein Mediated Toxicity in Mice. Neuroscience, 2020. 441: p. 58-64.

View the Full List of Publications

Lab Members
 

Hilary Grosso Jasutkar, MD, PhD
Dr. Grosso earned her PhD in neuroscience in 2012 and her medical degree in 2014, both at Rutgers – Robert Wood Johnson Medical School (RJWMS). She then completed a medical internship at Lankenau Medical Center, followed by a residency in neurology at Columbia University Irving Medical Center (CUIMC). After her residency training, Dr. Grosso completed a medical fellowship in the management of age-related disorders of cognition in the CUIMC Neurology Department’s Division of Aging and Dementia, during which time she worked as a post-doctoral fellow under the supervision of Dr. Ai Yamamoto at CUIMC. She then joined the Department of Neurology at Rutgers as a core member of the RWJMS Institute for Neurological Therapeutics in Neurology in 2021. In addition to her research, Dr. Grosso is a clinician who treats patients with age-related cognitive disorders. 

Azeez Ishola, PhD - Post-doctoral Associate
Dr. Ishola earned his doctoral degree in Anatomy at the University of Ilorin, Ilorin Nigeria. His doctoral research focused on the neurotoxicity of the psychoactive plant Datura metel, with keen interest on how one of the plant’s phytochemicals, datumetine, affects N-methyl-D-aspartate receptor (NMDAR) functions and behavior in mice. Currently he is working on the role of autophagy in synaptic function and how autophagic processes are altered in neurodegenerative diseases, focusing on Alzheimer’s disease. His hobbies include playing board games, reading, and visiting historical sites.

Contact the Lab
 

The Grosso Lab
Research Tower II/School of Public Health
683 Hoes Lane West
Piscataway, NJ 08854

To discuss our research, inquire about opportunities for collaboration, or if you are interested in joining our lab, please contact Dr. Grosso at hg381@rwjms.rutgers.edu.