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Oklahoma State University

Rudra Bhowmick

Research Assistant ProfessorRudra Bhowmick

Rudra.Bhowmick@okstate.edu

 

ACADEMIC BACKGROUND
Ph.D., Biochemistry, Jadavpur University, India, 2009
Postdoc, Tufts University School of Medicine, Boston, MA

Postdoc, University of Massachusetts Medical School, Worcester, MA
 

MAJOR AREAS OF RESEARCH
• Developing a 3D tissue engineered model of the human lung
• Studying stem cell differentiation in the lung
• Developing a nanoparticle-based drug delivery system for ocular applications

• Engineering a bioreactor to generate lung resident immune cells

 

RECENT RESEARCH ACTIVITIES

Developing a 3D tissue engineered model of the human lung

At present, most lung biology studies use cells cultured in monolayers (the so-called “2D cultures”), or mouse models. However, these models do not mimic the human lung physiology. While there are fundamental differences between the murine and human immune systems; the 2D-cultured cells lack the in vivo distribution of biochemical signals. We have used tissue engineering approaches to develop a 3D Human Tissue-engineered Lung Model (3D-HTLM) as a new platform to study cell behavior and immune responses in the lung. We engineered the 3D-HTLM by co-culturing at least 3 different types of human primary lung cells within a biodegradable scaffold (which we have developed). Apart from co-cultures, the 3D-HTLM also supports the culture of single cell populations. Our studies with human primary small airway epithelial cells cultured in the 3D-HTLM showed that the cells were more viable and showed in vivo-like cellular distribution and morphology in the 3D-HTLM. The 3D-HTLM also closely recapitulates the human immune responses to influenza A virus and can differentiate between pandemic and seasonal flu strains from the immune perspective. We are in the process of using this model to study lung responses to other viral infections, such as respiratory syncytial virus. In the long run, we expect this model to have wide-ranging applications from inflammation studies to therapeutics testing. This NIH-funded project is in collaboration with Drs. Lin Liu and Jerry Ritchey at OSU, and is part of the Oklahoma Center for Respiratory and Infectious Diseases.

 

Studying stem cell differentiation in the lungs

The lung has a sizeable number of stem cells, which when required, can differentiate into immune cell populations, such as alveolar macrophages (AMs). These stem cell-derived immune cells, along with the lung resident immune cells, play key roles in disease resolution. We are interested in the process by which stem cells transform into immune cell populations (such as AMs and dendritic cells, or DCs). We use the above-mentioned 3D-HTLM as a model to study stem cell differentiation. In recent experiments, we have added CD34+ hematopoietic stem cells (HSCs) to the 3D-HTLM and found that the HSCs differentiate into lung resident AMs and DCs. We are in the process of understanding and fine tuning this differentiation process. Once complete, the 3D-HTLM may be used as a platform to generate AMs and DCs specific to the lung milieu. This project is in collaboration with Dr. Susan Kovats, Oklahoma Medical Research Foundation and is funded by the Oklahoma Center for Adult Stem Cell Research.

 

Developing a nanoparticle- based drug delivery system for ocular applications

Non-invasive treatments for ocular diseases, such as macular degeneration and diabetic retinopathy, are currently difficult to achieve, as there are no reliable strategies to ensure continuous drug delivery to the affected areas. Our goal is to develop a nanoparticle-mediated drug delivery system, which would overcome this problem and deliver drugs to the inflamed area over an extended period of time. We have engineered drug-loaded nanoparticles and loaded them onto collagen membranes that can attach to contact lenses. Recent work includes studying the drug release kinetics from the nanoparticle/membrane constructs. We are also studying the effect of the nanoparticle/membrane constructs and released drugs on cultured human corneal epithelial cells.  In the long run, this work has the potential to emerge as a potent drug delivery option for several ocular diseases for which sustained drug delivery is critical.

 

Engineering a bioreactor to generate lung resident immune cells

In the body, immune cells can differentiate into other immune cell types. This differentiation is contingent upon the prevailing physiological conditions in the capillaries, such as circulatory flow and the presence or absence of inflammation. Our goal is to engineer bioreactors that can mimic the physiological environment of the capillaries and can act as a source for such cellular differentiation. We have devised a plate bioreactor and have cultured human primary capillary endothelial cells in it under media flow, to mimic the human capillaries. Currently, we are studying how human monocytes differentiate into DCs of multiple lineages within this bioreactor. We have also devised a tubular bioreactor and are in the process of characterizing endothelial cells cultured within the bioreactor. This project is funded by Oklahoma Health Research.

 

RECENT PUBLICATIONS

A complete list is available here

https://scholar.google.com/citations?user=xGXUveAAAAAJ