Labs
Our clinical research programs are active and growing rapidly. Our transplant nephrologists are actively involved in clinical transplantation research, particularly in the area of tolerance, in collaboration with faculty members in the Departments of Surgery and Microbiology-Immunology.
Learn more about the work conducted by labs within our division.
Daniel Batlle LabFocusing on the renin angiotensin system as it relates to the understanding of human diabetic kidney disease and rodent models of diabetic kidney disease and hypertension
Focusing on the renin angiotensin system as it relates to the understanding of human diabetic kidney disease and rodent models of diabetic kidney disease and hypertension
Research Description
Dr. Batlle’s lab currently focuses on the renin angiotensin system as it relates to the understanding of this system in rodent kidney physiology. Of particular focus are the pathways and mechanisms that determine the enzymatic cleavage and degradation of Angiotensin II and other peptides within the system by ACE2-dependent and independent pathways. The lab uses a holistic approach involving ex vivo, in vitro and in vivo studies using various rodent models of diabetic and hypertensive kidney disease.
The lab is also involved in the search for biomarkers of kidney disease progression as part of the NIDDK Consortium on CKD. Other areas of research interest include nocturnal hypertension and the physiology and pathophysiology of electrolyte disorders such as distal renal tubular acidosis.
For more information, please see Dr. Batlle's faculty profile.
Publications
See Dr. Batlle's publications in PubMed.
Contact
Contact Dr. Batlle. Paul DeCaen LabStudying ion channel relevance in cell biology and disease progression
Studying ion channel relevance in cell biology and disease progression
Research Description
We study the biophysics, pharmacology and physiology of ion channels. Currently, we are focused on two divergent groups: voltage gated sodium channels (Nav) and Polycystin channels (also called Polycystic Kidney Disease Proteins, PKDs). Aside from these foci, we actively explore novel ion channels found in prokaryotic and eukaryotic cells with the goal of understanding their function in cell physiology.
Current Projects
Voltage Gated Sodium Channels
Navs conduct sodium ions into excitable cells like muscle and neurons, causing the cell membrane to depolarize on the microsecond time scale, a process essential for rapid communication in multicellular organisms. Potentially fatal conditions such as forms of epilepsy and cardiac arrhythmias arise when Navs are mutated.
With our collaborators, we continue to examine key questions:
- How do these transmembrane proteins sense electrical potential and change from nonconductive to conductive states?
- How do these transmembrane proteins select for sodium ions and not allow passage of the other ions present?
- What are the mechanisms of action of clinically relevant drugs (e.g. Valproate and Lamotrigine) and where are their receptor sites?
Polycystin Channels and Primary Cilia
Mutations in PKD1 and PKD2 are associated with Autosomal Dominant Kidney Disease (ADPKD). ADPKD is one of the most common monogenetic diseases in mankind, where progressive cyst formation results in kidney failure. Several members of the polycystins (PKD1, PKD1-L1, PKD2 and PKD2-L1) have been found in the primary cilia from cells of various tissues besides the kidney. The primary cilium is a solitary, small (5-15 mM in length) protuberance from the apical side of polarized cells.
With help from our collaborators, our research is directed to answer key questions:
- How do ADPKD mutations alter PKD2 function? Do some mutations ‘turned on’ while others ‘turn off ’ the PKD2 channel?
- How does PKD1/2 channel dysfunction result in cyst formation? Or conversely, what normal function do they serve for the primary cilium and how do PKDs maintain cell polarity?
- What are the receptor sites within PKD2s that can modulation its ion channel function and are they drug-able?
For lab information and more, see Dr. DeCaen's faculty profile and lab website.
Publications
See Dr. DeCaen's publications on PubMed.
Contact
Contact Dr. DeCaen at 312-503-5930.
Postdoctoral Fellows: Orhi Esarte Palomero, Louise Vieira
Graduate Students: Eduardo Guadarrama, Megan Larmore
Research Staff: Victoria Pappas
Nicolae Valentin David LabMolecular mechanisms of metabolic bone diseases, with particular emphasis on the regulation and function of FGF23 in situations of normal and abnormal mineral metabolism.
Molecular mechanisms of metabolic bone diseases, with particular emphasis on the regulation and function of FGF23 in situations of normal and abnormal mineral metabolism.
Dr. David uses a basic science and translational research approach to characterize molecular events that are involved in the expression, post-translational modifications and secretion of the bone hormone FGF23 that is highly elevated in patients with chronic kidney disease (CKD). A major area of his research focuses on investigating a novel mechanism by which inflammatory signals and iron deficiency, common consequences of CKD, regulate FGF23. Our data show that acute inflammation stimulates FGF23 production, but simultaneous increases in FGF23 cleavage maintain normal levels of biologically active protein. However, chronic inflammation and sustained iron deficiency also increase biologically active FGF23, and show that these factors may contribute to elevated FGF23 levels in CKD.
Dr. David’s laboratory is funded by the National Institute of Health, National Institute of Diabetes and the National institute of Digestive and Kidney Diseases (NIDDK).
Email Dr. David
Faculty Profile
Tamara Isakova LabSpecializing in disordered mineral metabolism in chronic kidney disease; supporting a multi-center study testing the biochemical efficacy and safety of phosphates and FGF-23-lowering interventions in patients with stage 3-4 chronic kidney disease.
Specializing in disordered mineral metabolism in chronic kidney disease; supporting a multi-center study testing the biochemical efficacy and safety of phosphates and FGF-23-lowering interventions in patients with stage 3-4 chronic kidney disease.
Tamara Isakova, MD, MMSc, is leading an ancillary study within a multi-center pilot study that is funded by the U01 Consortium of Pilot Studies in chronic kidney disease (CKD). The parent study is designed to test the biochemical efficacy and safety of phosphate and FGF23-lowering interventions in patients with stage 3-4 CKD. The ancillary study supports baseline and follow up measurements of intermediate cardiovascular and renal end points. In addition to circulating biomarkers, Dr. Isakova is obtaining longitudinal measures of left ventricular mass using cardiac MRI and of renal oxygenation and fibrosis using BOLD MRI. To accomplish her aims, Dr. Isakova is working closely with investigators in the MRI imaging departments at Northwestern and NorthShore. Additional studies include ongoing investigations within large prospective cohort studies, including the CRIC Study.
Faculty Profile
Tamara Isakova, MD, MMSc Jing Jin LabSeeking to understand the molecular mechanisms of kidney and vasculature diseases.
Seeking to understand the molecular mechanisms of kidney and vasculature diseases.
The Jin lab is interested in understanding the molecular mechanisms of kidney and vasculature diseases. Cell junction and matrix proteins play a major role in the disease etiology and progression. We study how vascular and glomerular basement membrane (GBM) matrix proteins are interwoven, and the mechanisms for physiological and pathological GBM remodeling during repair. Specifically, we use mass spectrometry to map the patterns of post-translational modifications such as hydroxylation and glycosylation on the GBM collagen and study how these affect the meshwork topology. Ultimately we hope such knowledge may help to devise targeted therapies for a broad range of kidney and vascular diseases
The lab is generally interested in the pathological mechanisms of kidney and vascular diseases. We take a proteomic approach to study molecules that serve structural or functional roles in kidney filtration. Particularly, we are trying to understand how the kidney podocytes maintain and regulate their slit diaphragm, as well as their interactions with the glomerular basement membrane.
Faculty Profile
Pinelopi Kapitsinou LabExploring Oxygen-Sensing Pathways and Metabolism in Kidney Disease Development
Exploring Oxygen-Sensing Pathways and Metabolism in Kidney Disease Development
Research Description
The focus of our research is to understand how endogenous pathways governed by oxygen sensing mechanisms affect kidney disease development. In the kidney, low tissue pO2 levels arise because of limited oxygen supply by a specialized vascular network and high oxygen demands of tubular epithelium. Being particularly susceptible and responsive to hypoxia, the kidney serves as an ideal organ system to study adaptive and maladaptive effects of hypoxia signaling. The central mediators of systemic and cellular adaptation to O2 deprivation are hypoxia-inducible transcription factors HIF-1 and HIF-2, whose activity is negatively regulated by prolyl hydroxylase domain–containing enzymes (PHDs). The high complexity of the oxygen sensing machinery is illustrated by both canonical and non-canonical regulation, exhibiting distinct expression patterns within kidney tissue and evoking cell type- and context-specific responses. We have explored these molecular principles in acute kidney injury and during transition to chronic kidney disease. We have shown a critical role for endothelial PHD/HIF axis in post-ischemic kidney injury and fibrosis. Furthermore, we are particularly interested in investigating metabolic pathways that operate under the control of oxygen sensing. For example, we recently demonstrated a novel role for hypoxia in promoting tryptophan degradation, leading to enhanced generation of kynurenic acid and NAD+. By employing state-of-the art mouse genetics, single-cell transcriptomic and metabolomic approaches in both in vivo and in vitro systems, our research program aims to generate novel insights in kidney disease leading to discovery of novel therapeutic targets.
View Publications on PubMed
Contact: pinelopi.kapitsinou@northwestern.edu
Jennie Lin LabThe Lin lab studies the functional significance of human-based genomic and transcriptomic discoveries in cardiometabolic and kidney diseases.
The Lin lab studies the functional significance of human-based genomic and transcriptomic discoveries in cardiometabolic and kidney diseases.
Research Description
Elucidating How Genotype Lease to Phenotype in Cardiometabolic and Renal Disease
Unbiased human-based discovery efforts, such as genome-wide and exome-wide association studies, have identified many genetic loci for complex, disease-relevant traits. These genetics studies have provided invaluable data implicating novel loci in disease development and progression, but require functional follow-up to elucidate the mechanistic underpinnings driving the associated findings. A focus of the lab is to interrogate, through experimental wet-bench approaches, the functional significance of novel loci for blood lipids levels and measurements of renal function in the hopes of gaining new insights into pathways relevant to cardiometabolic and renal disease, respectively.
In particular, we are studying the role of A1CF, a gene encoding the RNA-binding protein APOBEC1 complementation factor and recently implicated as a locus for (1) elevated plasma triglycerides (Liu et al., Nature Genetics 2017), (2) estimated glomerular filtration fraction in non-diabetic individuals (Pattaro et al., Nature Communications 2016) and (3) serum urate (Kottgen et al., Nature Genetics 2013). We have already discovered that A1CF's actions extend beyond its canonical role of facilitating the editing of APOB mRNA, and we are currently integrating studies using animal and human cellular models to investigate how A1CF contributes to these associated traits.
Using iPSC and Genome Editing Technologies to Study Human Diseases
Although rodent models have contributed greatly to our understanding of human diseases, the genomic and physiologic differences between rodent and human have presented challenges in translating bench-based findings into clinic. To circumvent this roadblock, our lab is using iPSC-derived organoid models to study the effects of DNA variants within the native human genomic context. Using CRISPR-based technology to introduce or correct mutations in human iPSCs, we are modeling the effects of disease-associated mutations on cellular phenotype.
RNA-centric Approach to Studying Kidney Disease
Building upon A1CF-related work and previous experience with long non-coding RNA, we are studying the role of transcriptome-level regulation in the context of kidney disease. We have discovered that A1CF is a novel regulator of alternative splicing in both the liver and kidney, and we are currently working on how A1CF's regulation of splicing may influence intracellular metabolism. We are also studying how human-specific long non-coding RNAs influence gene expression and cellular phenotypes.
For more information, visit the Faculty Profile of Jennie Lin or visit the Lin Lab Website
Publications
See Dr. Lin's publications in PubMed.
Contact
Phone 312-503-1892
Aline Martin LabThe Martin Lab investigates the role of the skeleton in the endocrine regulation of mineral metabolism and the cardiovascular complications of mineral and bone diseases.
The Martin Lab investigates the role of the skeleton in the endocrine regulation of mineral metabolism and the cardiovascular complications of mineral and bone diseases.
Our research program focuses on the contribution of the skeleton to the mineral balance in the body. Bone produces a hormone, Fibroblast Growth Factor (FGF)-23, that participates in this balance. However in mineral metabolism disorders, such as in chronic kidney disease, the massive production of FGF23 is associated with negative outcomes and mortality. By understanding the mechanisms that control the production of FGF23, our goal is to develop new therapeutic strategies and improve outcomes in mineral metabolism disorders. To this goal, we perform basic and translational research using a combination of genetics, molecular biology, proteomics, histology and advanced imaging techniques.
A major focus of the lab is to investigate the transcriptional and post-translational regulation of FGF23 within the bone cells. In particular, we study the specific role of a known regulator of FGF23, Dentin Matrix Protein 1 (DMP1), on these regulations and on osteocyte biology in the context of diseases associated with FGF23 excess (chronic kidney disease, hypophosphatemic rickets …). A second focus is to investigate the mechanisms involved in negative outcomes associated with FGF23 excess, including bone mineralization defects, cardiac hypertrophy and cognitive defects. Our team works in collaboration with the Center for Translational Metabolism and Health and the Division of Cardiology at Northwestern, and with multiple additional collaborators and partnerships around the world.
The Martin Lab is sponsored by the National Institute of Health, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and by the Northwestern Women’s Health Research Institute.
Publications
For more information view Dr. Martin's Faculty Profile or view publications by PubMed
Contact Us
Contact Dr. Martin at 312-503-4160 or the Martin Lab at 312-503-4805, or by email.
Rupal Mehta LabInvestigating disordered phosphate homeostasis and the pathogenesis of microvascular disease in chronic kidney disease.
Investigating disordered phosphate homeostasis and the pathogenesis of microvascular disease in chronic kidney disease.
Rupal Mehta, MD is an assistant professor in the Department of Medicine, Division of Nephrology and Hypertension and a core faculty member in the Center of Metabolism and Health within the Institute of Public Health and Medicine. Under the mentorship of Drs. Myles Wolf and Tamara Isakova, Dr. Mehta is studying microvascular disease in the retina in chronic kidney disease (CKD) to more broadly understand the pathogenesis of microvascular disease and its impact on cardiovascular burden in CKD. She is conducting ongoing investigations in multiple large cohort studies including the Chronic Renal Insufficiency Cohort (CRIC) Study, Multi-Ethnic Study of Atherosclerosis (MESA), and the Beaver Dam Eye Study. As a member of the Center of Metabolism and Health, Dr. Mehta aims to advance her training in epidemiologic and patient-oriented research with the goal of building an academic career centered on research that informs improvements in care of patients with CKD.
Faculty Profile
Guillermo Oliver LabExploring how each specific cell type and organ acquires all its specific and unique morphological and functional characteristics during embryogenesis
Exploring how each specific cell type and organ acquires all its specific and unique morphological and functional characteristics during embryogenesis
Research Description
The Oliver Lab focuses on understanding how each specific cell type and organ acquires all its specific and unique morphological and functional characteristics during embryogenesis. Alterations in the cellular and molecular mechanisms controlling organ formation can result in major defects and pathological alterations. Our rationale is that a better knowledge of the basic processes controlling normal organogenesis will facilitate our understanding of disease. Our goal is to dissect the specific stepwise molecular processes that make each organ unique and perfect. Our major research interests are the forebrain, visual system and the lymphatic vasculature and to address those questions we use a combination of animal models and 3D organ culture systems, stem cells and iPS cells.
Related to the lymphatic vasculature, our lab identified years ago the first specific marker for lymphatic endothelial cells and generated the first mouse model devoid of lymphatics. We have characterized many of the critical steps leading to the formation of the lymphatic vasculature. We have also reported that a defective lymphatic vasculature can cause obesity in mice and we are currently trying to determine whether this is also valid in humans.
In case of the central nervous system, our focus is to characterize how complex structures such as the forebrain and eye are formed. For that we have started to apply 3D organ culture systems derived from stem cell and iPS that allow us to grow eyes in a petri dish. Using this approach we expect to dissect the genes and mechanisms controlling these developmental processes.
For more information, visit Dr. Oliver’s faculty profile or visit the Guillermo Oliver Lab Site.
Publications
View Dr. Oliver's publications at PubMed
Contact
Phone 312-503-1651
Joo-Seop Park LabKidney development and disease: How cell identities are determined by signaling pathways and transcription factors
Kidney development and disease: How cell identities are determined by signaling pathways and transcription factors
Research Description
The Park lab studies how stem/progenitor cells differentiate into specific cell types using the mouse kidney as a model system. The nephron, the functional unit of the kidney, is composed of at least 15 distinct cell types. Since all of the cell types found in the nephron originate from the common nephron progenitor cells, the mouse kidney serves as an excellent system to study cell fate decisions of stem/progenitor cells. We aim to (1) determine the roles of developmental signaling pathways in nephron formation, (2) identify transcription factors that define cell identities for each cell type found in the nephron, and (3) elucidate how these transcription factors coordinate with signaling pathways in gene regulatory networks.
For lab information and more, see Dr. Park's faculty profile.
Publications
See Dr. Park's publications on PubMed.
Contact
Contact Dr. Park
Susan Quaggin LabUncovering the molecular mechanisms of diabetic vascular complications, thrombotic microangiopathy, glomerular diseases and glaucoma
Uncovering the molecular mechanisms of diabetic vascular complications, thrombotic microangiopathy, glomerular diseases and glaucoma
Our lab focuses on the basic biology of vascular tyrosine kinase signaling in development and diseases of the blood and lymphatic vasculature. Our projects include uncovering the molecular mechanisms of diabetic vascular complications, thrombotic microangiopathy, glomerular diseases and glaucoma. Utilizing a combination of mouse genetic, cell biologic and proteomic approaches, we have identified key roles for Angiopoietin-Tie2 and VEGF signaling in these diseases. Members of the lab are developing novel therapeutic agents that target these pathways.
For more information, please see the faculty profile of Susan Quaggin, MD
Publications
See Dr. Quaggin's publication in PubMed