Summer Research Opportunities

Jeffrey Beamish, MD, PhD

Assistant Professor of Nephrology, Department of Internal Medicine

Our laboratory studies kidney regeneration. Acute kidney injury is a common condition associated with significant morbidity, mortality, and cost. Remarkably, kidney cells that are damaged in the most common forms of severe kidney injury can regenerate. However, no treatments are currently available that encourage this regeneration, in part because the mechanisms that control this process remain poorly understood. Likewise, efforts to develop bio-artificial kidney technologies have been limited by an inability to regenerate functional kidney cells outside of the body. Our research aims to understand the molecular and genetic regulators that govern kidney regeneration and exploit this knowledge to develop new therapeutic approaches to treat kidney injury and to engineer new technologies that promote regeneration of functional kidney tissue ex vivo.

Celine Berthier, PhD
Associate Research Scientist, Nephrology, Department of Internal Medicine

As member of the Michigan Kidney Translational Medicine Core (https://miktmc.org/), the major research interest of Dr. Berthier is lupus nephritis (LN); one of the main complications of systemic lupus erythematosus (SLE). She uses state-of-the-art tools to study new specific therapeutic opportunities in human LN, as well as new biomarkers for clinical disease stage or outcome and improve disease classification. She works in closed collaboration with Dr. Kahlenberg, rheumatologist, as well as with Dr. Gudjonsson, dermatologist at the University of Michigan, whose research interest is skin lesions in lupus patients. Their common goals are to understand the molecular mechanisms leading to lupus skin disease and the events driving the associated kidney disease. In this new area of single cell transcriptomics associated to disease mechanism discoveries, Dr. Berthier is interested in identifying renal and urine LN (specific) cell-lineage transcriptional signatures using translational methods.

Markus Bitzer, MD
Associate Professor of Nephrology, Department of Internal Medicine

Glomerular hypertrophy and podocytes stress lead to decreased podocytes density and are hallmarks of many glomerular diseases, in particular diabetic nephropathy and age-associated glomerulosclerosis. My research is focused on understanding the underlying molecular mechanisms of podocytes stress. We are integrating morphometric and transcriptomic data from human and mouse kidneys and validate our findings in tissue culture and animal models of kidney disease and injury. A particular focus is on non-coding RNAs including microRNAs, which are small non-coding RNAs that regulate expression post-transcriptionally and can be targeted with small molecules. We have identified specific microRNAs for which the expression in glomeruli is significantly associated with clinical outcomes and morphometric parameters of glomerular injury in patients with diabetic nephropathy and age-associated glomerulosclerosis. To explore the function of these microRNAs, we inhibit or overexpress these microRNAs in cultured glomerular cells (mesangial cells and podocytes) and determine the effect on cell survival, proliferation, extra-cellular matrix production and cytoskeleton structure.

Charles Burant, MD, PhD
Professor of Metabolism, Endocrinology and Diabetes (MEND), Department of Internal Medicine

The Burant lab is studying the development of diabetic kidney disease in both rodents and humans. We are studying the relationship between increased blood glucose and changes in cellular metabolism, including changes in mitochondrial function through modifications of proteins. We use metabolomic profiling to determine the changes in the flux of metabolites through various pathways. We also use computational tools to understand the changes in intermediary metabolism in diabetes.

Mona Doshi, MD
Professor of Internal Medicine

Live kidney transplant is the preferred choice of treatment for a patient with advanced kidney disease. While this surgery definitely helps the recipient (both medically and in the longevity and quality of life), it also provides the donor with personal satisfaction. My research focuses on improving the medical and psychosocial evaluation of live kidney donors so that they can continue to enjoy a healthy life after donation. This summer, we will leverage the University of Michigan’s live kidney donor transplant database to assess the impact of their pre-donation demographic and clinical characteristics on post-donation outcomes. For example we can assess the effect of history of opioid use, obesity, mental health, etc. on medical & psychosocial well-being after surgery.

Greg Dressler, PhD
Collegiate Professor of Pathology Research

The Dressler lab studies the embryonic development and the genes that control cell fate determination.  How embryonic genes are reactivated and impact disease is also of interest.  Much of the work focuses on kidney and renal epithelial cells.  We have discovered several new genes and pathways which can be manipulated to suppress renal injury and to enhance recovery.  Student can contribute to ongoing projects in genetically engineered mouse models of kidney disease using biochemical, immunological, and cell biological methods to address function.

Evan Farkash, MD, PhD
Assistant Professor, Department of Pathology

Antibody mediated rejection (AMR) is a major cause of late graft loss after kidney transplantation, but the existing criteria for AMR diagnosis suffers from poor sensitivity.  Recognizing patients who are at risk for graft failure would permit improved targeting of patients for therapy or recruitment into clinical trials.  Using targets identified in molecular expression analysis, we are developing new tissue-based biomarkers for AMR, testing the utility of computer aided-diagnosis using digital morphometric analysis and comparing them with primary and secondary clinical endpoints.  Possible translational projects for students include collecting manual morphometric data, digital morphometry, and/or multivariate analysis to identify biomarkers associated with AMR and poor outcome.  Students will be mentored in renal pathology and the use of database/statistical software, and will become familiar with renal histology and patterns of renal transplant rejection.

Puneet Garg, MD, FASN
Assistant Professor of Nephrology, Department of Internal Medicine

Over the past decade, identification of human diseases with podocyte-specific gene mutations and observations from animal models and cell culture studies have led to intense scientific interest in the role of podocytes in glomerular diseases.  Nephrin and Neph1 are cell adhesion molecules of the Ig superfamily that are specifically targeted to podocyte intercellular junctions. When deleted in human inherited disease or in mouse genetic mutant models, absence of Nephrin or Neph1 result in a developmental phenotype in which podocyte tertiary process formation and podocyte intercellular junction is dramatically disrupted, suggesting that these proteins are required for normal podocyte patterning. Investigation of the signaling mechanisms by which nephrin and neph1 influence podocyte process patterning and cell junction formation revealed their ability to assemble a protein complex that can regulate actin cytoskeletal dynamics. My lab is interested in the signaling mechanisms responsible for Nephrin phosphorylation and regulation of podocyte actin dynamics. We are also interested in studying mechanisms by which endocytosis of membrane proteins including Nephrin influences podocyte homeostasis. As Nephrin is also expressed in pancreas, we are investigating its role in insulin vesicle secretion in the pancreas by generating a mouse model where Nephrin will be conditionally deleted in the pancreatic beta cells.

Debbie Gipson, MD, MS
Associate Professor of Pediatric Nephrology, Department of Pediatrics

Kidney disease will affect up to 1 in 9 North Americans during their lifetime. When prevention, early diagnosis and treatments fail, kidney failure may occur which requires life-saving therapies with dialysis or kidney transplantation. Our research team studies one of the leading causes of kidney failure, namely glomerular diseases. Opportunities for summer projects included use of an electronic health record data set to evaluate the prevalence, therapies and health outcomes of children and adults with glomerular disease at UM and participate in the linkage of these data with 2 other large academic health systems in the USA.

Jeff Hodgin, MD, PhD
Assistant Professor, Department of Pathology

Computer-assisted and automated image analysis of the kidney biopsy. The Hodgin lab focuses on the molecular and cellular features of glomerular disease. The glomerulus is a complex, specialized filtration unit made up of three cell types – endothelial cells, mesangial cells, and podocytes. Qualitative and semi-quantitative assessment of injury in kidney biopsies through evaluation of structural and cellular alterations in glomeruli has been a crucial part in the diagnosis and treatment decisions in patients with glomerular disease. Our lab is working to improve this by adding quantitative pathology through the use of image analysis software designed by information technology specialists in the Department of Pathology. For example, podocyte loss has been identified as a driving force in disease progression across nearly all glomerular diseases. In collaboration with the Wiggins lab, we are designing methods to measure podocyte density in kidney biopsies fast enough to be a part of the clinical workflow. We are also analyzing cellular features of glomeruli in a cohort of patients with lupus nephritis to determine clinically useful parameters. A student project would help design and validate cutting-edge software algorithms to quantitate cellular and structural characteristics of diseased glomeruli. In addition, quantitative kidney pathology data will be analyzed in larger patient cohorts with glomerular transcriptomic data to identify key molecular pathways in the progression of glomerular disease.

Ken Inoki, MD, PhD
Associate Professor of Life Sciences Institute, Molecular & Integrative Physiology, and Nephrology, Department of Internal Medicine

The Inoki lab is investigating the function and regulation of nutrients-sensing kinases such as mTOR (mechanistic/mammlian target of rapamycin) and AMPK (AMP-activated protein kinase) in the development of kidney diseases such as diabetic nephropathy. Both mTOR and AMPK sense intracellular nutrient levels to control essential anabolic (i.e. protein and lipid biosynthesis) and catabolic (i.e. autophagy) processes. We have recently identified that aberrant activation of mTORC1 in podocytes (glomerular epithelial cells) occurs in both type1 and type2 diabetic kidney in human and animal models. Aberrant activation of mTOR or insufficient activation of AMPK leads to podocyte injury and contributes to the development of diabetic nephropathy. However, the molecular mechanisms by which mTORC1 is up-regulated and mTORC1 activation causes podocyte injury under diabetic conditions remains elusive. Using biochemical and genetic approaches, our research focuses on investigating signal transductions from nutrients (i.e. glucose and amino acids) in cultured podocytes and the roles of these signals in the development of podocyte injury and diabetic nephropathy using mouse models.

Wenjun Ju, PhD
Associate Research Scientist, Nephrology, Department of Internal Medicine, Department of Computational Medicine and Bioinformatics (DCMB) and Michigan Diabetes Research and Training Center

Chronic kidney diseases (CKD) affect 13% of adult population in the United States. Patients with CKD can progress into end-stage renal disease (ESRD) requiring dialysis and renal replacement therapy, associated with high cost, morbidity and mortality. Disease progression can be delayed or halted and patient outcomes can be improved if early detection and treatment becomes possible. By applying systems biology approach in CKD, we are able to pinpoint the candidate non-invasive biomarkers, whose expression in kidney can predict kidney function and kidney disease progression (for more information: http://stm.sciencemag.org/content/7/316/316ra193). Our current research focuses are: validation of the candidate non-invasive markers in the urine samples of international large cohorts of CKD patients; determination of the pathophysiology role of validated biomarkers in disease initiation and progression; and developing novel therapeutic strategies to prevent CKD progression.

Matthias Kretzler, MD
Professor of Nephrology, Department of Internal Medicine,  and Computational Medicine & Bioinformatics

The research in Dr. Kretzler’s team focuses on the analysis of molecular mechanism of glomerular failure. Using integrated biology approaches the group defines transcriptional networks in human glomerular diseases and integrates them with complex clinical data sets and other large-scale data sets. The NEPTUNE network offers the unique opportunity to analyze a prospective cohort of glomerular disease patients with high-resolution clinical and molecular phenotyping.  An international multi-disciplinary research team will enable large scale data integration across the genotype-phenotype continuum of glomerular failure with carefully monitored environmental exposures, genetic predispositions, epigenetic markers, transcriptional networks, proteomic profiles, metabolic fingerprints, digital histological biopsy archive and prospective clinical disease characterization.
Opportunities for bioinformatics graduate student rotations include integrative analyzes across species along the genotype-phenotype continuum in an interdisciplinary research team.

Possible projects include work on strategies for (1) integrating systems information into genetic association analyses, (2) identifying molecular subsystems affected by multiple candidate genetic variants, and (3) identifying shared mechanisms across tissues, species, or phenotype.

Expansion of the project into a Ph.D. thesis is possible and funds for support might be available. 
Background in analysis of large-scale data sets is preferred; basic concepts of molecular biology, statistics and programming are preferred; and ability to function and interact in a multidisciplinary team is essential.

Laura Mariani, MD
Assistant Professor of Nephrology, Department of Internal Medicine

Nephrotic Syndrome is caused by several diseases that result in a similar patient presentation of massive proteinuria, edema, hypoalbuminemia and hyperlipidemia. The complications that patients experience result not only from the disease process (kidney failure, clotting and edema) but also side effects from the immunosuppressive therapies that we give them. Unfortunately, even within a particular pathologic disease, such as focal segmental glomerulosclerosis (FSGS), there is tremendous heterogeneity in patient presentation, response to therapy and prognosis. My research interest is in helping to evaluate whether novel clinical features, biomarkers or gene expression patterns can better help inform patient prognosis and response to therapy by identifying clinically relevant subgroups.

The summer project will leverage the Nephrotic Syndrome Study Network (NEPTUNE), a unique, multi-center, prospective cohort of 500 patients with minimal change disease, membranous nephropathy and focal segmental glomerulosclerosis who are enrolled at the time of diagnostic kidney biopsy. Using a broad dataset which includes clinical information, tissue gene expression, urinary biomarkers and pathology descriptors, we will evaluate potential predictors of disease progression and response to therapy.

Anna Mathew, MD
Assistant Professor of Nephrology, Department of Internal Medicine.

Chronic kidney disease (CKD) affects ~15% of adults in the U.S and is a risk factor for cardiovascular disease (CVD). CVD is prevalent in nearly 40% of CKD patients contributing to more than 10-fold CVD mortality compared to healthy controls. Thus, even though we are able to prolong patient’s life after their kidneys fail with dialysis or kidney transplant, these patients ultimately die of accelerated heart disease. Since traditional risk factors are unable to completely explain the aggressiveness of the heart disease in kidney patients. Our work examines the causes and mechanisms behind the disproportional risk of heart disease in kidney patients. Dr. Mathew’s project aims to explore the role of immune metabolism and activated immune cells in the development of heart disease in kidney patients. We propose to use a very sensitive and state of the art mass spectrometry platform to detect these changes in patients with increased heart disease and kidney disease in both clinical studies and animal models. Identifying the mechanism behind this increased heart disease risk will create new drugs and lifestyle changes so that kidney patients can have a longer heart disease-free life.

Subramaniam Pennathur, MD
Professor of Nephrology, Department of Internal Medicine

The central theme of the Pennathur research group has focused on the applications of biological mass spectrometry in disease pathogenesis. A major focus of the lab has been to define the metabolic basis of diabetic complications, chronic kidney disease and cardiovascular disease. We have utilized mass spectrometry to identify key protein and metabolite alterations in disease states and tested the hypothesis whether or not these alterations predict complications in animal models and humans. Our strategy has been to develop analytical techniques in animal models and validate these markers in humans and then interrogating the animal model for biological pathway relevance. Recent extensions of this work have included targeted as well as untargeted metabolomics and proteomic profiling and systems integration to identify disease mechanisms. 

Jeffrey L. Platt, MD
Professor of Surgery, and Microbiology and Immunology

Cellular and Molecular Biology of kidney disease, transplant rejection and cancer.  For nearly one hundred years, the kidney has been considered one of the main targets of immune and inflammatory reactions.  Although we are born with a surfeit of kidney tissue and function, kidneys are the first organs to "wear out" with aging.  Kidneys are compromised in part by immunity and inflammation occurring in other parts of the body and over time.  This problem is amplified in kidney transplants. In the course of research directed at understanding the distinct properties of immune and inflammatory reactions that evoke renal disease, Dr. Platt and members of his laboratory discovered that far from being a passive target, the kidney (and other organs) acquire resistance to immune and inflammatory reactions, a condition Dr. Platt named accommodation.  Accommodation was first described in kidney transplants but it is now apparent that all tissues and organs as well as tumors can accommodate to immunity, inflammation and other forms of injury.  Dr. Platt investigates the cellular and molecular mechanisms of accommodation in renal transplants and tumors, genetic changes that modify accommodation reactions and long-term consequences of accommodation reactions in the kidney and other organs.  Recent work has led to novel therapeutics that might promote accommodation in transplants and undermine it in cancer.  

Bruce Robinson, MD, MS
Vice President for Research, Arbor Research, Adjunct Clinical Assistant Professor of Internal Medicine, Division of Nephrology

Dr Robinson is Principal Investigator of the Dialysis Outcomes and Practice Patterns Study (DOPPS) Program at Arbor Research. Now in 20+ countries, the DOPPS Program includes our longstanding international prospective cohort study of hemodialysis patients (DOPPS, since 1996), and our newer cohort studies in peritoneal dialysis (PDOPPS) and advanced chronic kidney disease (CKDopps). Research focuses on characterizing practice variation and identifying practices associated with the best patient outcomes, with the goal of improving patient longevity, quality of life, and other outcomes. Supervised research activities will focus on data analysis and critical review, and can also include participation in design and implementation of our new international projects.

Rajiv Saran, MD, MBBS, MS, MRCP 
Professor of Internal Medicine, Division of Nephrology, Associate Director, UM Kidney Epidemiology and Cost Center (UM-KECC)

Dr. Rajiv Saran, MBBS, DTCD, MD, MRCP (UK), MS, the Florence E. Bingham Professor, Division of Nephrology, Department of Internal Medicine, at University of Michigan (UM) and . UM School of Public Health, and plays a leadership role at University of Michigan’s Kidney Epidemiology and Cost Center (KECC). Dr. Saran is an internationally recognized expert in kidney disease surveillance. Until very recently (2014 – 2019) he served as Director of the prestigious United States Renal Data System (USRDS). Since 2006, he has been Co-Principal Investigator for the Centers for the Disease Control and Prevention’s (CDC’s) National CKD Surveillance System for the US, a one of a kind project that focuses on upstream surveillance of CKD and its risk factors. From 2012-2016 Dr. Saran led the development of the first National Kidney Disease Information System (VA-REINS), for the Department of Veterans Affairs (VA), funded by the VA’s Center for Innovation. Dr. Saran has recently (2018-2020) been funded on a spin off project from VA REINS for investigation of hot-spots of kidney disease among US Veterans involving both risk-prediction and geospatial analyses. He also serves as Co-Principal Investigator for a cluster randomized, pragmatic trial (DIALYSAFE) in hemodialysis aimed at improving cardiovascular safety, funded by the Patient Centered Outcomes Research Institute (PCORI).