Research Junction Connecting Faculty Across Campus

1.     What is your educational background?

I obtained my master’s degree in Zoology from Andhra University, Visakhapatnam, India, and a Ph.D. from Central Drug Research Institute, Lucknow/Dr BR Ambedkar University, Agra, India. Later I pursued postdoctoral studies in osteoimmunology at École Normale Supérieure de Lyon, Lyon, France followed by a second postdoc on cellular interactions and development at Institut de Recherches Cliniques de Montréal, Montréal, Canada.

2.     Where is your hometown?

I am from Kakinada, Andhra Pradesh, India. Kakinada is a seaport in the southeast of India and a mid-sized town with a 300,000 population.

3.     Why did you choose MUSC?

Following my postdoctoral studies, I moved to the University of Kentucky at Lexington as a senior research associate where I had the opportunity to work with Drs. Jeffrey Ebersole and Sarandeep Huja on host immune response and bone loss in periodontal disease. Dr. Huja (then-incoming Dean of the College of Dental Medicine at MUSC) recruited me to the University. MUSC is a unique academic health science center with comprehensive medical and health care research portfolios and an ideal place to pursue my own translational and drug discovery research.

4.     What are your current research interests and how did you become interested in this field?

I have extensive training in the pathophysiology of bone and reproductive endocrinology. I pursued anti-estrogens and several new chemical entities for treating postmenopausal osteoporosis during my doctoral studies. Among bone cells, osteoclast biology has been my favorite and I decided to pursue my career studying it. During my postdoctoral training, I conducted investigations on the role of specific cytokines (CXCL8, CXCL13), tyrosine kinase Hck, and adaptor proteins (DAP12) on osteoclast differentiation in the broader contexts of osteoimmunology and cancer biology. After moving to MUSC, I embarked on a new area to understand the tumor microenvironment (TME). Tumors are heterogeneous organs, with diverse stromal components and the TME of head and neck squamous cell carcinoma (HNSCC) is unique with fibroblasts, immune cells, and other supporting cells. Mutations in the cancers, such as alterations to TP53, PI3K, PTEN, and specific gene expression profiles, contribute to derangements in cancer and microenvironment cells such as overproduction of chemokines, increased ROS, and epithelial to mesenchymal transition. I am currently investigating how immune cells and tumors interact and how productive and non-productive anti-tumor immune responses affect the development of cancer. In addition, we are interested in understanding the role of other innate immune cell types such as macrophages in the recognition of tumor lesions and adaptive anti-tumor immunity. I am also interested in oral biology projects particularly on host immunity and inflammatory response that determines the susceptibility to develop destructive/progressive periodontitis. Individuals with periodontal disease (PD) present with a complex array of inflammatory mediators and cellular infiltration by immune cells. I am actively investigating how chronic exposure to pathogenic bacterial components affects and contributes to PD, and specifically the downstream development of a macrophage immune response to PD-associated bacteria.

5.     What has been your biggest scientific contribution to date?

I am always excited about my research projects and I have thrilling results from my current work. However, I consider my biggest contribution to date would be my postdoctoral research on OSTM1/gray lethal (gl) mutations. OSTM1/Ostm1 mutations are responsible for the most severe form of osteopetrosis and neurodegeneration in humans and mice, both resulting in early death. The gl gene is widely expressed in several hematopoietic lineages including the osteoclasts, brain, spleen, thymus, and melanocytes, consistent with the different pathologies detected in the Ostm1-null gray lethal mouse mutant (gl/gl). Transgenic expression of Ostm1 in multi‐hematopoietic lineages of the gl/gl mice rescued all the hematopoietic defects. Of interest, we were able to show astrogliosis, microgliosis, and severe neuronal death in Ostm1 transgenic mice on gl/gl genetic background. Targeting of Ostm1 to different brain cell lineages in the gl/gl mice, we were able to demonstrate that only the neuron-specific Ostm1 transgenic mice led to full brain defect complementation consistent with neuronal defects detected in human OSTM1 osteopetrosis. Interestingly, Ostm1 is a type I single transmembrane protein with the transmembrane region encoded by exon 5. The first well‐defined human OSTM1 osteopetrotic mutation is an in‐frame deletion of exon 5 encoding the transmembrane region, indicating a key membrane‐associated role. A large part of the Ostm1 protein is luminal, highly glycosylated, and localized to the endoplasmic reticulum, trans‐Golgi network, and endosomes/lysosomes. We also established that Ostm1 is a part of cytosolic multiprotein complex and interacts directly through the carboxy- and trans-membrane regions with the motor protein Kinesin 5B (KIF5B). I was fortunate to contribute to this work and my former postdoc lab is actively pursuing the specific role of Ostm1 in the individual hematopoietic cells and/or lineages.

6.     Is there a scientific area/field you would like to know more about?

Expertise in oncology and immune cell biology would be an asset to thoroughly understanding the tumor microenvironment. I am currently collaborating with Drs. Shikhar Mehrotra and Terrence Day (from the College of Medicine) to explore TME in HNSCC and Dr. Nancy DeMore to understand drug resistance in breast tumors. Furthermore, I am actively working with Drs. Ozlem Yilmaz, Sarandeep Huja, Pinar Emecen-Huja, and Hong Yu (from the College of Dental Medicine) on oral biology projects addressing how chronic exposure to TLR activators affect macrophage recruitment and differentiation in periodontal disease. I am open to discussions and look forward to creating new collaborations with MUSC researchers in these domains.

7.     Would you like to connect with colleagues within a certain field? If so, what field/area?

Inflammatory bowel disease and ulcerative colitis research. As I expand my research into the field of osteoimmunology, collaborations with scientists focused on IBD and colitis would be exciting. I have some interesting ideas in these inflammatory disease and sepsis areas and look forward to forming fruitful collaborations.

8.     What are some of your hobbies? What do you do for fun?

I like listening to Indian classical music and love reading about horology and “green power” or clean energy solutions.

9.     What is your favorite movie, tv show, food?

I am a fan of Harry Potter's wizarding world and Spielberg's "Jurassic Park." Not much into TV shows but I like Kenneth Branagh's "Wallander" series. Food: Being an Indian and a vegetarian, I like our cuisine mostly and have some appetite for Italian too.

10.  Please share one interesting detail about yourself.

Not sure if there is something interesting about me. I have good baking skills and dream of having my own bakery one day.

11.  If you had a yacht, what would you name it?

Perseverance, after US's latest Mars rover. I was very impressed to read a seventh grader's essay which made him win the "name the rover" contest.

12.  Who would play you in a movie about your life?

Very interesting thought, not sure this will ever come true. For thought sake, I would love to get Daniel Radcliffe for the role.

13.  If you were not a scientist, you would be:

I would have ended up being a production supervisor at an Indian pneumatic tyre manufacturing facility.

14.  What are the top three activities on your bucket list?

I would like to (i) visit Nordic countries, (ii) visit the International Watch Museum at La Chaux-de-Fonds, Switzerland and (iii) learn how to kayak.

15.  What’s the best advice you were ever given?

My college teacher once told me, "Don’t worry about what people say about you. When you are successful, they are talking about you, and when you're not, they're still talking about you, so just go ahead and do what seems right to you." His advice gave me confidence and has fortified me thus far.

Make a Connection

Drop Dr. Subramanya Pandruvada an email at pandruv@musc.edu