July 2017 spotlight of the month
Nitin Kumar, PhD., Postdoctoral Fellow, Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, MI-48202
- How did you become interested in research relating to Hypertension?
I have always been interested in studying the mechanisms involved in hypertension and cardiovascular disease, ever since I was an undergraduate student back at home in Delhi, India.
However the real opportunity to conduct experiments in hypertension research came when I met my current mentor and renowned renal physiologist Dr. Oscar A. Carretero at Hypertension and Vascular Research Division in Henry Ford Hospital, Detroit, USA.
Under his mentorship, I had the opportunity of learning and studying renal and non-renal mechanisms involved in high blood-pressure and its related end-organ damage in animal models.
- Describe your research & the program/lab (info of your supervisor) that you are in?
High blood-pressure affects ~30% of the world population and numbers are increasing every year. Hypertension imposes a major threat of developing heart, kidney and brain damage and contributes to the increased morbidity and mortality in human patients.
My supervisor Dr. Carretero and his laboratory are interested in studying the mechanisms of cardio- and reno-protective effects by the naturally-occurring small peptide named N-Acetyl-Seryl-Aspartyl-Proline (Ac-SDKP) and its precursor peptide thymosin b4 in hypertension-induced end organ damage. Ac-SDKP is a natural substrate for Angiotensin Converting Enzyme (ACE) and ACE inhibitor treatment increases plasma and urinary Ac-SDKP concentration 4-6 folds.
Our group has reported that some of the beneficial effects of ACE inhibitors in hypertension and cardiovascular diseases are in part due to an increase in Ac-SDKP concentration. Our laboratory has conducted extensive research in the past decade and found the beneficial therapeutic effects of Ac-SDKP in the heart and kidney of animal models such as in Dahl salt-sensitive hypertensive rats, spontaneously hypertensive rats, experimentally induced-heart failure and autoimmune diseases. These beneficial effects of Ac-SDKP are mediated in part by reducing tissue infiltration of macrophages and T-cells, and reducing collagen synthesis without affecting the blood-pressure.
Another area of research that I am interested in is the identification of an unknown peptidase that participates in the release of Ac-SDKP from its precursor thymosin b4.
- What do you consider to be your substantial scientific contribution so far (provide Pubmed PMID if possible)?
Our laboratory has previously shown that Ac-SDKP exerts anti-inflammatory properties in hypertension; however the enzymatic pathways by which anti-inflammatory peptide Ac-SDKP is synthesized in the body was not clear. During my postdoctoral training, I identified the involvement of the peptidase meprin-a (highly expressed in the brush-border of the renal proximal tubule) together with second enzyme prolyl-oligopeptidase in the release of Ac-SDKP from its precursor thymosin b4.
Kumar, N.; Nakagawa, P.; Janic, B.; Romero, C. A.; Worou, M. E.; Monu, S. R.; Peterson, E. L.; Shaw, J.; Valeriote, F.; Ongeri, E. M.; Niyitegeka, J. M.; Rhaleb, N. E.; Carretero, O. A., The anti-inflammatory peptide Ac-SDKP is released from thymosin-beta4 by renal meprin-alpha and prolyl oligopeptidase. American Journal of Physiology. Renal Physiology 2016, 310, (10), F1026-34. PMID:26962108
- What is your favourite manuscript from a lab or mentor other than your own (provide Pubmed PMID if possible)?
One of my favourite manuscripts is from the interesting work performed by Dr. John R. Vane and his fellow K.K.F.Ng that showed the conversion of Angiotensin-I to Angiotensin-II that took place in the lungs. I liked the methodology used by John R. Vane to collect arterial and venous blood from the lungs and then measure the rat colon contraction. They found that the contractor activity of the endogenous angiotensin was significantly increased after passage through the pulmonary circulation.
Ng, K. K.; Vane, J. R., Conversion of angiotensin I to angiotensin II. Nature 1967, 216, (5117), 762-6. PMID: 4294626
- What facilities are essential for your research?
There are several factors that are essential for my research which include but are not limited to Innovative ideas, troubleshooting, excellent team work, dedication and hard work, and, of course, funding and support from the federal agencies.
- Where do your research strengths lie? Why? What are your research weaknesses? How will you improve?
My research strengths are the skills and expertise acquired during my research career in my PhD and in postdoctoral work. I received excellent training in performing experiments related to biochemistry, molecular biology, immunology and animal physiology. I have also developed critical thinking, innovative ideas, and the ability to generate hypotheses for grants-writing.
I would like to work in translational research, so that I can contribute to advancing the findings and discoveries of basic research into clinics. I could overcome this limitation by collaborating and working with physician scientists.
- Describe your unforgettable (proudest) moment in science, and the most challenging situation that you have had to overcome (lessons learnt) so far?
It may sound strange to some but one of my unforgettable moments in science was when I saw the proteins running in SDS-PAGE gel with blue loading-dye and rainbow marker during my bachelor’s courses. We all have read the theory of SDS-PAGE technique in the chromatography books but it was so satisfying when I saw it for the first time and then successfully did it by myself after 5-6 times of failure.
I would like to share one more unforgettable moment in science. I was learning animal surgery during my postdoctoral training to insert catheter tubing in the femoral artery and vein in the rats for blood pressure monitoring. It felt so difficult and at one point I thought I would not be able to do this. However, after repeated failures and continued practice, I was finally able to insert the femoral artery and vein catheter successfully.
- At which conference did you first present? How was your experience?
My PhD is in protein biochemistry, from Verona University, Italy. The first conference I presented at was the 7th European Biophysics Congress held in Genoa, Italy in 2009. I had the wonderful opportunity of meeting outstanding researchers in the field.
At the same meeting, I met Dr. Martin Chalfie, who won the 2008 Nobel Prize for Chemistry for his contribution and development of Green Fluorescent Protein. These scientific talks and knowledge gave me strength and enthusiasm to pursue a career in science.
- What upcoming conferences will you be attending, and what is the furthest distance that you have traveled for a conference?
I will be attending the American Heart Association Council on Hypertension in September 2017, and the American Society of Nephrology Kidney Week in November 2017.
The furthest I have traveled to attend a conference was from Detroit, MI to San Diego, CA for the Experimental Biology meeting in 2016.
- How did you learn about ISH/NIN and its activities?
I learned about ISH from one of my colleagues, Dr. Cesar A. Romero, at the Hypertension Division, Henry Ford Hospital.
- What area(s) do you wish to specialize in the future?
In the future I would like to specifically focus on the renovascular genetic and molecular mechanisms contributing to high blood pressure-induced vascular and organ damage.
- Who is your role model in Science? Why?
My role model is my current mentor Dr. Oscar A. Carretero. He played a key role in contributing significantly to our current knowledge of the Kallikrein-Kinin System. He was the first person to show the source and localization of kallikrein peptidase in the distal segment of the Nephron.
- What are your scientific goals? Advice for talented emerging scientists?
My scientific goal is to provide new insights in identifying novel mechanisms involved in hypertension and cardiovascular diseases by employing biochemical, molecular and immunological tools. I believe that through my research I can significantly advance the current knowledge in hypertension, which may help to improve the lives of all people with high blood-pressure related morbidity.
My advice for talented emerging scientists is to stay focussed, work hard, read papers to understand the current research in your field, develop innovative ideas and critical thinking and ask questions even if you think they are stupid. My mentor always says that the only stupid question is the one that you don’t ask!