PKD research fellowships

To move us forward in finding treatments, we select outstanding researchers as recipients of the PKD Foundation Fellowships. The fellowships recognize early-career scientists whose achievements and potential identify them as rising stars – the next generation of scientific leaders in PKD research. Each fellow receives $60,000 a year for two years.

2019 fellows

Harini Ramalingam, Ph.D.

University of Texas Southwestern Medical Center

Project Summary

Investigating the m6A RNA Methylation Pathway as a Therapeutic Option for ADPKD Treatment

ADPKD is a genetic disease characterized by the growth of numerous fluid-filled cysts in the kidney. Currently, ADPKD is a leading cause of kidney failure. The goal of my project is to find therapeutic targets that can treat ADPKD. We have identified that a novel biochemical pathway called m6A RNA methylation, is elevated in human ADPKD and multiple mouse models of ADPKD. Through genetic modulation of this pathway, we are able to reduce disease progression in one ADPKD mouse model. Next, my aim is to determine whether this pathway is a common mode of disease pathogenesis in clinically-relevant ADPKD models. Recent evidence shows that m6A RNA methylation affects the abundance of proteins. I will employ a cutting-edge technology called Ribo-seq and bio-informatic tools to identify all the actively processed proteins, which are regulated by this RNA modification pathway and are key players of ADPKD progression.

Biography

I received a Bachelor's degree in Computer Science and a Master's in Biological Sciences from Birla Institute of Technology and Science, India in 2009. I received my doctoral degree from the University of Texas Southwestern Medical Center in 2017. I finished my dissertation studies under the tutelage of Dr. Thomas Carroll. My dissertation title was "Balancing Renewal and Differentiation of Progenitor Cells in the Developing Kidney". I joined Dr. Vishal Patel's lab in 2018 for postdoctoral research training. My research is focused on understanding RNA metabolism in ADPKD progression and kidney development.

Venkata Vivek Reddy Palicharla, Ph.D.

University of Texas Southwestern Medical Center

Project Summary

Role of Tulp3-mediated ciliary protein trafficking in kidney cystogenesis

PKD is characterized by the presence of multiple large cysts in kidneys. These cysts result in an abnormal increase in the size of the kidneys, ultimately leading to kidney failure. Only one drug is available to treat PKD. Therefore, it is important to do more research on PKD to develop better treatment strategies. The first step in this process is to understand how kidney cysts are formed. Cells in kidneys have small appendages called primary cilia which are involved in sensing the environment and regulating multiple cellular functions. Earlier research has implicated the involvement of cilia in PKD pathogenesis. Through our research, we aim to understand how protein transport into and out of the cilia regulates cyst formation and test if any of these processes can be of therapeutic potential.

Biography

Dr. Palicharla is a post-doctoral fellow under the mentorship of Dr. Saikat Mukhopadhyay in the Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX. He is currently working on understanding the role of protein trafficking to primary cilia in polycystic kidney disease. He earned his Ph.D. from Centre for DNA Fingerprinting and Diagnostics (CDFD) (Manipal Academy of Higher Education), India, where he worked on identifying novel cellular roles of non-canonical ubiquitin linkages.

Rebecca Walker, Ph.D.

University of Maryland

Project Summary

Relieving the Stress of PKD: A new role of PKHD1 in detoxification mediated via differential cleavage of the intracellular domain

ARPKD is a severe disease causing cyst-development throughout the kidneys. ARPKD is caused by mutation in the PKHD1 gene. The child mortality rate is high, therefore current treatment focuses on addressing severe symptoms in childhood. Patients surviving the first year of life have poorly functioning kidneys and often require extensive hospital treatment. Our knowledge of mechanisms underlying ARPKD cyst-development is greatly lacking. There is a real need for research to understand the fundamental properties of the proteins and mechanisms underlying ARPKD. Our lab has found a possible link between PKHD1 protein and detoxification of harmful chemicals in the kidney. We believe that PKHD1 protein is processed to produce fragments that move around inside kidney cells and activate pathways which warn the cell of toxins. Success in this investigation will transform our understanding of cyst-development in PKD and provide potential innovative targets for patient treatment.

Biography

Dr. Walker received her Bachelor of Science degree from The University of Leicester in the UK where her love for genetics flourished. She went on to receive her PhD from Oxford University in the UK, performing research which began her career in the field of Polycystic Kidney Disease, under the mentorship of Dr. Dominic Norris. She has undertaken important research discussing the significance of Polycystin 2 localization to cilia, a cellular organelle. Upon moving to the USA, she began her postdoctoral research in the Laboratory of Dr. Feng Qian and has expanded her interest to include investigating ARPKD. She has become intrigued by the mechanisms involved in maintaining a healthy tubule architecture and discovering which of these are disrupted in Polycystic Kidney Disease.

2018 fellows

Bruno Balbo, M.D., Ph.D.

Yale University

Project Summary

Targeting the Cell Cycle as a Potential Treatment for ADPKD: the Role of Cyclin-dependent kinase 1

In this study, we will investigate the biological mechanisms in which an essential cell cycle regulator, the Cyclin dependent kinase 1 (Cdk1), interferes with renal disease progression in PKD models. We will focus on how cyst initiation and progression are affected through the subcellular evaluation of cell cycle markers, expression of regulatory proteins and protein-protein interactions. In addition, we will also test the effectiveness of pharmacologic inhibition of the FoxM1 transcriptional factor, a regulator of Cdk1, on halting disease progression. Elucidating the pathogenic mechanisms that link cell cycle regulation, ciliary abnormalities and disease progression in ADPKD could provide a translational basis for potential clinical studies.

Biography

Dr. Balbo is a nephrologist trained at University of São Paulo, Brazil, where he completed a Ph.D. investigating cardiovascular complications in PKD. In 2017 he moved to the USA to undertake a post-doctoral fellowship under the guidance of Dr. Stefan Somlo at Yale School of Medicine.

Kai He, Ph.D.

Mayo Clinic

Project Summary

Restoring ciliary level of functional polycystins as a novel therapeutic approach for ADPKD treatment

ADPKD is the most common inherited renal disorders. Polycystin 1 and polycystin 2, encoded by the causal genes PKD1 and PKD2, have been proposed to form a receptor/channel complex on kidney epithelial cilia. Accumulating evidence suggest a link between the level of functional polycystins and disease severity, indicative of a dosage model of cystogenesis. We recently discovered a novel paradigm that axoneme polyglutamylation is essential for the ciliary anchoring of polycystins. In this proposal, we will molecularly dissect the pathways regulating axoneme polyglutamylation and the ciliary localization of polycystins. We will further explore if restoring ciliary polycystins, by genetically or pharmaceutically targeting key regulators in glutamylation machinery, will suppress the development of PKD. An imaging-based high-content screening will be further used to discover more promising hits that could restore ciliary polycystins. Accomplishing this project will significantly advance our understanding of polycystin biology, and providing novel therapeutic avenues for ADPKD.

Biography

I received Doctoral degree from the Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences in biochemistry and molecular biology in 2016. During my Ph.D. training, I worked on studying the mechanisms of cell death-survival determination and cell differentiation. Particularly, I studied the molecular connection between mitochondrial dysfunction and epithelial-mesenchymal transition (EMT) in cancer progression, and the molecular bases of cell fate determination during TGF--induced simultaneous apoptosis and EMT. I moved to Mayo Clinic in 2016 for postdoctoral research training. My current research direction is focus on cilia signaling and ciliopathies, especially autosomal dominant polycystic kidney disease (ADPKD). I focus on how the PKD proteins and other cilia-related signaling machineries properly localize to cilia to execute the sensory function. My long term research goals are advancing the understanding of cilia biology and further identifying novel therapeutic approach/targets/hits that address unmet clinical needs of ciliopathies patients.

2017 fellows

Ashima Gulati, M.D.

Yale University School of Medicine

Project Summary

Genetic variants predisposing to intracranial aneurysm formation in autosomal dominant polycystic kidney disease

Biography

Dr. Gulati is a pediatric nephrologist with a medical degree from New Delhi, India and training in pediatrics and nephrology at University of Connecticut and Yale School of Medicine. Her research is part of the Investigative Medicine Ph.D. program at the Yale Graduate School of Arts and Sciences. Her mentor, Stefan Somlo, M.D., is director of the Center for Polycystic Disease Research at Yale School of Medicine.

Sara Holditch, Ph.D.

University of Colorado Denver Anschutz Medical Campus

Project Summary

PKD gene therapy targeting the 4E-BP1 pathway

Biography

Dr. Holditch earned a bachelor’s degree in microbial biology from the University of California, Berkeley and completed her Ph.D. in virology and gene therapy at the Mayo Clinic Graduate School of Biomedical Sciences. She has authored 19 publications, (six as first author). Her research is under the mentorship of Charles Edelstein, M.D., Ph.D., an internationally known expert in biomarkers of kidney disease and PKD.

Yan Zhang, Ph.D.

University of Kansas Medical Center, the Kidney Institute

Project Summary

Targeting the LKB1-AMPK signaling pathway in polycystic kidney disease

Biography

Dr. Zhang earned her B.S. in pharmacy at Sichuan University, a M.S. in pharmacology at Peking Union Medical College and Ph.D. in pharmacology and toxicology at University of Missouri-Kansas City. She is pursuing post-doctoral training under the mentorship of Darren P. Wallace, Ph.D., at the University of Kansas Medical Center.

2015 fellows

Marcelo Cassini, M.D., Ph.D.

Yale University School of Medicine

Project Summary

Can Mcp1 knock-out and blockage of macrophage receptor CCR2 alter the outcome of polycystic kidney disease?

Biography

Dr. Cassini earned an M.S. degree in kidney transplantation and a Ph.D. in kidney injury from the University of Sao Paulo – Brazil. He received his medical degree at Federal Fluminense University in Rio de Janeiro – Brazil and completed residency training in surgery and urology at State University of Rio de Janeiro. His research is under the guidance of mentor Lloyd Cantley, M.D., at Yale School of Medicine. Read more about Dr. Cassini

Whitney Besse, M.D.

Yale University School of Medicine

Project Summary

Genetic mechanisms of cyst pathogenesis in polycystic liver and kidney diseases

Biography

Dr. Besse earned a bachelor’s degree in biomedical engineering from Brown University, a medical degree from the University of Connecticut School of Medicine, and completed residencies in internal medicine and nephrology at the Yale School of Medicine. Her mentor, Stefan Somlo, M.D., is director of the Center for Polycystic Disease Research at Yale School of Medicine. Read more about Dr. Besse

Jeong-In Baek, Ph.D.

Medical University of South Carolina

Project Summary

The role of Tuba in ciliogenesis and cytogenesis

Biography

Dr. Baek is a post-doctoral fellow in the Department of Medicine, Medical University of South Carolina in Charleston. She earned a bachelor’s degree in biology, a master’s degree in molecular biology, and a Ph.D. in human genetics from Kyungpook National University in South Korea. She has authored over 21 publications (nine as first author). Her research is under the mentorship of Joshua Lipschutz, M.D., internationally known expert in renal ciliogenesis and PKD.

Jacqueline Peda, Ph.D.

University of Kansas Medical Center

Project Summary

The regulation of cardiac remodeling by PC1 and SMYD1 in polycystic kidney disease

Biography

Dr. Peda earned her B.S. in biology at Washburn University, and an M.S. and Ph.D. in pathology at the University of Kansas Medical Center. She is pursuing post-doctoral training under the mentorship of Dr. Xiaogang Li at the University of Kansas Medical Center.

Irfana Soomro, MBBS

New York University Langone Medical Center

Project Summary

Targeting glutamine metabolism as a potential treatment for ADPKD

Biography

Dr. Soomro earned her MBBS (bachelor of medicine/surgery) at Dow Medical College – Karachi, Pakistan. She is a clinical instructor in the division of nephrology at New York University Langone Medical Center, Bellevue Hospital Medical Center. Her research is under the mentorship of Edward Skolnik, M.D., director of the Division of Nephrology.