(2ba) Biomolecular Interactions and Transport Laboratory (BIT Lab) to Create a Transformative Impact on Human Health.

Curing Alzheimer's disease or predicting whether the next revolutionary drug molecule can be manufactured relies on unraveling the mechanisms governing the transport and interactions of biomolecules with their surroundings. My Biomolecular Interactions and Transport (BIT) laboratory will use experiments, flow computations, and theory to address such grand challenges in physiological fluid transport, disease diagnostics, and pharmaceutical manufacturing. My research training is in the fields of interfacial sciences, experimental and physiological fluid mechanics, soft matter biophysics, rheology, microfluidics, and mouse models of disease. Building on these foundations, my research group will engineer micro and macroscale systems to study diseases caused by protein aggregation, test new treatments, and develop a biophysics-informed framework to predict the manufacturing success of protein-based drug molecules. We will work on:

1. Disease diagnosis in physiological systems: My group will develop microfluidic and organ-on-a-chip systems to study how neurotoxic proteins aggregate in the body, causing diseases like Alzheimer’s and Cerebral Amyloid Angiopathy. We will use the in vitrodisease-on-a-chip models to predict how physiological flows and age-related changes in the cellular microenvironment trigger "hot spots" of protein deposition in the brain. Such studies could bring new insight into the mechanisms that cause Alzheimer's disease and related dementias. In the long term, the predictive models and technology developed will also serve as a testing platform for new therapies that restore cellular function.

2. Biomolecular stability in manufacturing systems:My research group will engineer scaled-down models of pharmaceutical manufacturing unit operations to predict the aggregation and stability of protein-based therapeutics, such as monoclonal antibodies (mAbs). Aggregated mAbs can significantly affect drug potency and elicit adverse reactions during administration. We will investigate the bulk rheology, interfacial rheology, and aggregation mechanisms of mAbs solutions by combining experiments and flow computations with protein-specific in-situ fluorescence, light scattering, and spectrophotometric tools. We will use this integrated approach to develop state-of-the-art predictive mechanistic models that isolate the contributions of the different destabilizing manufacturing forces. Adopting such biophysics-based models to predict stability, instead of ad-hoc solutions currently employed by the industry, will help reduce wastage, improve manufacturing efficiency, and ultimately lower the cost of bio-therapeutics.

Teaching Interests:

At the undergraduate level, I am prepared to teach various foundational engineering courses, with a preference for Transport Phenomena and Engineering Laboratory courses. At the more advanced level, I am interested in teaching courses that cover the principles of Soft Matter, Colloids and Interfacial Sciences, Transport in Non-Newtonian Fluids, Rheology of Complex Fluids, and Biological Fluid Mechanics.

Honors and Awards

• Steadman Family Postdoctoral Associate Prize in Interdisciplinary Research (2021)
• University of Rochester Career Development Award, 2020

Select Publications (out of 10):

1. Raghunandan, A., et al. "Cervical Lymphatic Drainage is impaired in old age and restored with Prostaglandin-2α" (Accepted at Nature Communications)
2. Raghunandan, A., et al. "Bulk flow of cerebrospinal fluid observed in periarterial spaces is not an artifact of injection." eLife10 (2021): e65958.
3. Raghunandan, A., et al. "Predicting steady shear rheology of condensed-phase monomolecular films at the air-water interface." Physical Review Letters16 (2018): 164502.