Center/Research Area Affiliations

• Cornea Center of Excellence
• Ocular Regenerative Medicine Institute

Biography

At Schepens Eye Research Institute of Mass. Eye and Ear, Dr. Chauhan’s research interests focus on immunomodulation and regenerative medicine for ocular surface injury and inflammatory disorders. His work has led to many important novel findings, including loss of function of regulatory T cells (Tregs) in corneal transplantation and the involvement of highly pathogenic Th17 cells in the immunopathogenesis of dry eye disease.

More recently, Dr. Chauhan has focused on using immunomodulatory and regenerative functions of Mesenchymal Stem Cells (MSCs) to treat ocular surface disorders. His research has recently demonstrated that MSCs have the capacity to restore corneal transparency by secreting high levels of hepatocyte growth factor. Dr. Chauhan is studying the function of immunoregulatory cells, including MSCs, Tregs, and myeloid suppressor cells, with the ultimate goal of using their therapeutic potential in ocular inflammation.

Dr. Chauhan is also Affiliate Faculty at Harvard Stem Cell Institute. 

Immunomodulatory and Regenerative Functions of Mesenchymal Stem Cells in Ocular Injuries and Inflammation

The goal of this project is to identify and use the immunomodulatory and regenerative functions of mesenchymal stem cells (MSC) to treat ocular surface disorders. Since their discovery, MSCs have held tremendous promise for tissue regeneration, primarily due to their differentiation capacity. However, this represents only a portion of the vast potentials of MSCs in re-establishing tissue homeostasis, including their capacity to promote immune quiescence.

Little is known how MSCs modulate the host immune response. Although MSCs have been shown to suppress pathogenic immune cells, the specific molecular mechanisms by which MSCs directly promote the function of regulatory immune cells remain much less understood.

Dr. Chauhan is exploring the molecular mechanisms by which MSCs promote function of critical regulatory immune cells. In the setting of ocular inflammation and immunity, he is investigating how MSCs (1) promote generation of myeloid suppressor cells and (2) enhance the function of regulatory T cells.

His results from animal models of corneal injury (IOVS 2012, Stem Cells 2017) and transplantation (IOVS 2014) suggest that the immunomodulatory function of MSCs could effectively be used therapeutically. His is also evaluating the capacity and mechanisms of MSCs in restoring corneal transparency. Ocular injuries involving the cornea undergo a wound healing process that often results in scar formation and loss of corneal transparency. Dr. Chauhan has reported that MSCs are capable of restoring corneal transparency. Specifically, he has shown that (1) MSCs secrete high levels of hepatocyte growth factor (HGF), which inhibits the generation of opacity-inducing myofibroblasts and (2) that HGF alone can restore corneal transparency in an in vivo model of corneal stromal injury, suggesting a novel HGF-based therapeutic approach that could potentially eliminate the need for cell-based and conventional therapies (Stem Cell Reports 2016, Molecular Therapy 2017).

Dr. Chauhan believes that MSC-based treatments (cell-based or identified factors) could be a significant improvement over the current use of non-specific anti-inflammatory and immunosuppressive drugs, which are fraught with serious side effects.

Regulation of Innate Immune Responses in Ocular Injury

Eye injuries due to trauma, infection, and burns are common causes of ocular inflammatory disorders and blindness worldwide. Following injury, innate immune responses—primarily through recruitment of activated neutrophils to the eye—lead to deleterious inflammatory tissue damage and fibrosis. As neutrophils advance from the vasculature to the site of injury, they go through progressive stages of activation and release effector molecules, including tissue matrix-destructing enzymes myeloperoxidase (MPO) and N-elastase (ELAN).

Current treatments, such as steroids, not only suppress the protective immune response non-specifically, but are also associated with serious side effects, including infection, cataract, and glaucoma. Thus, there is a pressing need for new therapeutic strategies that can regulate innate inflammation by selectively inhibiting pathogenic neutrophil effector function.

Dr. Chauhan’s pilot studies indicate that during ocular inflammation, infiltrating neutrophils interact with non-hematopoietic tissue-resident stromal cells. These eye-resident stromal cells effectively regulate neutrophil effector functions, including the release of tissue-destructing MPO and ELAN. In this project, using a standard mouse model of ocular injury and a series of novel experiments, he is delineating critical mechanisms by which stromal cells regulate neutrophil effector function and promote reestablishment of immune quiescence in ocular inflammation.

Dynamics of Treg and Th17 Cells in Ocular Immunity

This project aims to determine the role of regulatory T cells (Tregs) and pathogenic Th17 cells, and their secreted cytokines in the induction of antigen-specific immunity and tolerance—both in corneal transplantation and autoimmune dry eye disease. His work has led to many important novel findings. He has reported the involvement of highly pathogenic and autoreactive Th17 cells in the immunopathogenesis of dry eye disease. Using a murine model of dry eye disease, he clearly demonstrated that in vivo inhibition of Th17/IL17 pathway leads to amelioration of both the induction and progression of the disease (J Immunol, 2009; Blood 2011). He also established that levels of Foxp3 in Tregs reflect their functional status in transplantation, and reported an association between Treg function and corneal allograft survival (J Immunol 2009; J Immunol 2014). He is now developing strategies for clinical translation of our novel research findings, particularly a Treg cell-based therapy to promote allograft survival and a Th17/IL17-antagonist-based immunotherapy for dry eye disease.

Current Members of Dr. Sunil Chauhan’s Laboratory

Administrative Coordinator

• Linda Benson

Senior Research Associate

• Sharad Mittal, PhD

Postdoctoral Fellows

• Afsaneh Amouzegar, MD
• Mingshun Li, MD
• Sayed Basiony, MD
• Sachin Shukla, PhD

Graduate Student

• Disha Singhania (U Cambridge)

Alumni

To date, more than six trainees have worked in Dr. Chauhan’s laboratory.