Selected Publications

Kalavalapalli S, Bril F, Koelmel JP, Abdo K, Guingab J, Andrews P, Li WY, Jose D, Yost RA, Frye RF, Garrett TJ, Cusi K, Sunny NE. (2018) Pioglitazone improves hepatic mitochondrial function in a mouse model of nonalcoholic steatohepatitis. Am J Physiol Endocrinol Metab. 315(2): E163-E173. PMID: 29634314.

Sunny NE, Bril F, Cusi K. (2017) Mitochondrial Adaptation in Nonalcoholic Fatty Liver Disease: Novel Mechanisms and Treatment Strategies. Trends Endocrinol Metab. 28(4): 250-260. Review. PMID: 27986466.

Patterson RE, Kalavalapalli S, Williams CM, Nautiyal M, Mathew JT, Martinez J, Reinhard MK, McDougall DJ, Rocca JR, Yost RA, Cusi K, Garrett TJ, Sunny NE. (2016) Lipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity. Am J Physiol Endocrinol Metab. 310(7): E484-94. PMID: 26814015.

Satapati S, Kucejova B, Duarte JA, Fletcher JA, Reynolds L, Sunny NE, He T, Nair LA, Livingston K, Fu X, Merritt ME, Sherry AD, Malloy CR, Shelton JM, Lambert J, Parks EJ, Corbin I, Magnuson MA, Browning JD, Burgess SC. (2015) Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver. J Clin Invest. 125(12):4447-4462. PMID: 26571396, PMCID: PMC4665800.

Sunny NE, Kalavalapalli S, Bril F, Garrett TJ, Nautiyal M, Mathew JT, Williams CM, Cusi K. (2015) Crosstalk between branched chain amino acids and hepatic mitochondria is compromised in nonalcoholic fatty liver disease. Am J Physiol Endocrinol Metab. 309(4):E311- E319. PMID: 26058864, PMCID: PMC4537921.

Satapati S*, Sunny NE, Kucejova B, Fu X, He T, Mendez-Lucas A, Shelton JM, Perales JC, Browning JD, Burgess SC. (2012) Elevated TCA cycle function in the pathology of diet induced hepatic insulin resistance and fatty liver. J. Lipid Res. 53(6) 1080-1092.  PMID: 22493093.

Sunny NE, Parks EJ, Browning JD, Burgess SC. (2011) Excessive hepatic mitochondrial TCA cycle and gluconeogenesis in humans with nonalcoholic fatty liver disease(link is external). Cell Metab.14: 804-810. PMID: 22152305; Highlighted by Nature Reviews Endocrinology, Mitochondrial pathways in NAFLD. Highlighted by Science Daily, Fatty livers are in overdrive.

Sunny NE, Bequette BJ. (2011) Glycerol is a major substrate for glucose, glycogen and non essential amino acid synthesis in late term chicken embryos. J. Anim. Sci. 89: 3945-3953. PMID: 21764833.

Sunny NE, Satapati S, Fu X, He T, Mehdbeigi R, Spring-Robinson CL, Duarte J, Potthoff M, Browning J, Burgess SC. (2010) Progressive adaptation of ketogenesis in mice fed a high fat diet. Am J Physiol Endocrinol Metab. 298 (6) E1226-35. PMID: 20233938; PMCID: PMC2886525

Sunny NE, Bequette BJ. (2010) Gluconeogenesis differs in developing chick embryos derived from small compared with typical size broiler breeder eggs. J. Anim. Sci. 88:912-921. PMID: 19966165

Sunny NE, Owens SL, Baldwin VI RL, El-Kadi SW, Bequette BJ. (2007) Salvage of blood urea nitrogen in sheep is highly dependent upon plasma urea concentration and the efficiency of capture within the digestive tract. J. Anim. Sci. 85:1006–13. PMID: 17202392

Bequette BJ, Sunny NE, El-Kadi SW, Owens SL. (2006) Application of stable isotopes and mass isotopomer distribution analysis to the study of intermediary metabolism of nutrients. J. Anim. Sci. 84(E. Suppl.):E50–9. PMID: 16582092

 

SZPZ2605 (2)
Nishanth E. Sunny, PhD Principal Investigator

With a degree in Veterinary Medicine from Kerala, India, Dr. Sunny came to University of Maryland, College Park in 2002 where he earned his M.S. (2005) and Ph.D. (2008) in Animal Nutrition, under the mentorship of Dr. Brian J. Bequette. Following a postdoctoral fellowship at the University of Texas Southwestern Medical Center, Dallas  (2008-2010) under Dr. Shawn C. Burgess, Dr. Sunny continued as a Research Assistant Professor (2012-2016) at the Division of Endocrinology, Diabetes, and Metabolism at University of Florida, Gainesville. Dr. Sunny is currently an Assistant Professor at the University of Maryland, College Park since Jan 2017. Dr. Sunny is interested in understanding the metabolic mechanisms modulating growth and development in various species, and also contributing to the etiology of obesity, insulin resistance, and fatty liver disease.

 

shafeekh
Muhammed Shafeekh Muyyarikkandy, PhD Postdoctoral Associate

Dr. Muyyarikkandy graduated with a degree in Veterinary Medicine from Kerala Veterinary and Animal Sciences University, India in 2013. He then joined the University of Connecticut in 2014 and earned his M.S. and Ph.D. in 2018 under the mentorship of Dr. Amalaradjou. His research was focused on studying the effect of probiotics in modulating in Salmonella pathogenesis. In addition, he received Northeast SARE graduate student research grant and investigated the impact of early in ovo probiotics administration to promote embryonic development and post-hatch growth of chickens. Dr. Muyyarikkandy started as a postdoctoral associate in Dr. Sunny lab in September 2018, where his research is aimed at understanding the role of mitochondrial dysfunction in the pathophysiology of liver diseases.

 

Chaitra
Chaitra Surugihalli, MS Doctoral Student

Following her Bachelors degree in Biotechnology from Visvesvaraya Technological University, Belgaum, India, Chaitra came to United States and completed her M.S. in Molecular Cell biology from University of Connecticut, Storrs. Chaitra’s research goal in the Sunny lab is to profile the metabolic adaptation of developing chicken embryos to neonatal chicks, with the objective of understands the regulatory aspects of mitochondrial metabolism and lipogenesis.

 

 

Christine Zhang
Christine Zhang Undergraduate Student

Christine is a sophomore pre-med undergraduate student pursuing a double major in Biochemistry and Neurobiology & Physiology.  As part of the Sunny Lab, she is gaining meaningful and interesting hands-on experience in the scientific research process. She hopes that her research experience will contribute to a more holistic view of scientific advancements in medicine. She enjoys learning new techniques and data analysis methods while working with other motivated lab members. She is currently working on analyzing mitochondria in mice models in order to better understand the onset and development of fatty liver disease. In her free time, Christine enjoys hiking with friends, running, and shadowing in the Emergency department at Prince George’s Hospital Center.

 

Vaishna Muralidaran
Vaishna Muralidaran Undergraduate Student

Vaishna is a junior undergraduate student earning her B.S in Neurobiology & Physiology with a minor in History. She just recently began working in the Sunny Lab and hopes that her time here will help her gain research skills that she can put towards her future endeavors outside of the University of Maryland. Vaishna is currently on the pre-med track and hopes to one day become an endocrinologist. In her free time, she enjoys watching movies, baking for her friends and family, and playing badminton.

 

 

 

nathan
Nathan Kattapuram Undergraduate Student

Nathan is a sophomore Neurobiology and Physiology major who joined the lab in November of 2018. He is interested in learning various techniques to investigate metabolic regulation in the body of an animal, and hopes to apply those principles to a career in medicine. In his free time, he enjoys playing the squash, learning new songs on the piano, and reading.

 

Sunny lab: Uncovering the Secrets of the Mitochondria

Mitochondria, considered the powerhouse of our cells, integrates nutrient metabolism and energy production to maintain normal cell function. Optimal mitochondrial function promotes growth and development, while mitochondrial dysfunction is a key feature of the metabolic diseases including obesity, diabetes and fatty liver. Sunny lab focuses on identifying strategies to enhance mitochondrial function targeted towards a) healthy growth and development and b) treatment of metabolic diseases. Sunny lab utilizes a variety of in vitro cell culture systems with in vivo animal models to tease out mechanisms regulating the mitochondrial function. These animal models include diet-induced/ transgenic mice models to probe mitochondrial dysfunction during metabolic disease and novel developing chicken embryo/ neonatal chick model to probe metabolic transition of mitochondrial networks during growth and development. Sunny lab profiles mitochondrial metabolism utilizing a combination of techniques including the state-of-the-art stable isotope based metabolic flux analysis, targeted metabolomics and tissue protein and gene profiling.

Sunny lab: Uncovering the Secrets of the Mitochondria

Mitochondria, considered the powerhouse of our cells, integrates nutrient metabolism and energy production to maintain normal cell function. Optimal mitochondrial function promotes growth and development, while mitochondrial dysfunction is a key feature of the metabolic diseases including obesity, diabetes and fatty liver. Sunny lab focuses on identifying strategies to enhance mitochondrial function targeted towards a) healthy growth and development and b) treatment of metabolic diseases. Sunny lab utilizes a variety of in vitro cell culture systems with in vivo animal models to tease out mechanisms regulating the mitochondrial function. These animal models include diet-induced/ transgenic mice models to probe mitochondrial dysfunction during metabolic disease and novel developing chicken embryo/ neonatal chick model to probe metabolic transition of mitochondrial networks during growth and development. Sunny lab profiles mitochondrial metabolism utilizing a combination of techniques including the state-of-the-art stable isotope based metabolic flux analysis, targeted metabolomics and tissue protein and gene profiling.

Project 1: To identify key mechanisms to attenuate unregulated mitochondrial metabolism in the liver, and thus provide a better paradigm to treat fatty liver disease and type 2 diabetes mellitus (T2DM). Hepatic insulin resistance is characterized by fat accumulation which progressively transform to nonalcoholic steatohepatitis (NASH), with inflammation and fibrosis. This major public health problem affects over 70% of the obese and T2DM patients. Defects in mitochondrial oxidative metabolism are central to the etiology of fatty liver disease. Uregulated activity of mitochondrial pathways can be a chronic source of free radicals and oxidative stress. We believe that mechanisms to abate unregulated mitochondrial metabolism will be of major benefit towards alleviating oxidative stress and inflammation during fatty liver disease.

Project 2: Regulation of mitochondrial metabolism and lipogenesis in embryonic to post-hatch chicken. The late term embryonic chicken (>day-16 of incubation) derives >90% of its energy through oxidation of yolk lipids in the liver. Furthermore, metabolic transition of an embryo to a neonatal chick is also associated with up-regulation of new lipid synthesis. Interestingly, despite this metabolic milieu favoring high rates of mitochondrial lipid oxidation and the dramatic up-regulation of lipid synthesis in the liver, the chicken embryo manages to efficiently transition and develop into a healthy hatchling. Thus, we believe that the embryonic to post-hatch transition period in chicken, is a novel model to investigate mechanisms balancing fat oxidation by the mitochondria and new lipid synthesis. Our long term goal is to develop a ‘dual-intent’ research program utilizing this model to a) probe the etiology of fatty liver disease and T2DM, and b) identify mechanisms for improving the metabolic efficiency during embryonic-neonatal transition: a question which is also of significant interest to poultry production and management.

Project 3: Modulation of mitochondrial function by branched chain amino acids (BCAAs) Branched chain amino acids (leucine, isoleucine, valine) are among the most responsive amino acids to insulin. Consequently disturbances in BCAA metabolism has been described in several insulin resistant states including obesity, diabetes mellitus, kidney and liver dysfunction. Defects in intracellular BCAA oxidation, particularly by muscle and adipose tissue is considered to be a major contributor to elevated plasma BCAAs during insulin resistance. These global changes in BCAA degradation and higher systemic BCAAs can impact the nutrient milieu available to the liver and alter mitochondrial metabolism. Degradation of BCAA proceeds through several acyl-CoA intermediates with the terminal products being acetylCoA, ketones and metabolic intermediates of TCA cycle. Further, BCAAs serve as major precursors for the synthesis of alanine and glutamine through transamination, mainly in the muscle and adipose tissue. The end products of BCAA degradation and nonessential amino acids are potential anaplerotic substrates (fuels) for hepatic TCA cycle. More importantly, BCAA have the ability to signal through a variety of molecular mediators of mitochondrial metabolism including mTORC1, AMPK, PGC1α and PPARα. Understanding mechanisms connecting BCAAs and hepatic mitochondrial function, in order to modulate growth and development and also to manage metabolic diseases, is our major objective .