Northwestern University Feinberg School of Medicine
Feinberg Cardiovascular Research Institute

Labs

Following are descriptions of the lab work done by center members, listed by principal investigator.

Please note that not all work done within these individual labs falls within the goals of the Center for Kidney Research and Therapeutics.

 M. Javeed Ansari Lab

Seeking an understanding of the mechanisms of transplant rejection and tolerance using animal models and clinical material.

Dr. Ansari’s Transplant Immunobiology Research Laboratory’s emphasis is on understanding the mechanisms of transplant rejection and tolerance using animal models and clinical material. Specifically, the research focus is Th 17 immunity, leukocyte recruitment and T cell exhaustion. Other research interests include understanding the specificity of the immune response and developing tools to monitor immune response specific to the transplant.

Faculty Profile

M. Javeed Ansari, MBBS

 Daniel Batlle Lab

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

Dr. Batlle

 Nicolae Valentin David Lab

The primary focus of Dr. David’s laboratory is to increase understanding of molecular mechanisms of metabolic bone diseases. In particular he studies 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).

Faculty Profile

Nicolae Valentin David, PhD

 Lorenzo Gallon Lab

Looking to improve outcomes in renal transplantation.

Dr. Gallon’s laboratory focuses on the following research areas:

  1. Understanding the effects of different immunosuppressive agents on subpopulation of human T and B cells by using in vitro culture systems, Flow cytometry and functional assays.
  2. Understanding the impact of modifications of maintenance immunosuppression on cellular and molecular Immune profiles in Renal Transplant Recipients
  3. Tolerogenic approaches to renal transplantation
  4. Primary FSGS (Focal Segmental Glomerulosclerosis)

Faculty Profile

Lorenzo Gallon, MD

 Tamara Isakova Lab

Specializing in disordered mineral metabolism in chronic kidney disease; supporting a multi-center study testing the biochemical efficacy and safety of phospates 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 Lab

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

Jing Jin, PhD

 Xunrong Luo Lab

Tolerance mechanisms in autoimmune diabetes and transplantation

Research Description

1.     Tolerance mechanisms for transplantation.  We use rodent as well as non-human primate models.  These models include allogeneic islet, heart and kidney, and xenogeneic islet transplantation. Transplant tolerance is induced by infusion of donor cells treated with the chemical cross-linker ethylcarbodiimide (ECDI).  Using a stringent full MHC-mismatched strain combination, we have shown in an allogeneic islet cell transplant model that two infusions of ECDI-treated donor cells prior to and after transplantation led to indefinite graft survival in over 90% of the transplant recipients in the absence of any immunosuppression.  This tolerance strategy takes advantage of the tolerogenic recognition of apoptotic donor cells by recipient CD11c dendritic cells, and is associated with up-regulation of Tregs and down-regulation of anti-donor T and B cell responses.  The same strategy has been applied to allogeneic heart and kidney transplant, as well as xenogeneic islet transplant (rat-to-mouse, pig-to-mouse) with robust tolerance efficacy.  We are currently applying the same strategy to monkey-to-monkey (allogeneic) and pig-to-monkey (xenogeneic) islet transplantation.  Our ultimate goal is to test this tolerance strategy in human-to-human (allogeneic) and pig-to-human (xenogeneic) solid organ and/or tissue transplantation.  Additional ongoing efforts in the lab also focus on: (1) understanding how viral infections at various stages (acute, chronic, latent) can influence tolerance efficacy and stability; (2) collaborating with Shea lab in designing nanoparticle-based cell-free tolerance strategies for allogeneic and xenogeneic transplantation.

2.  Proteins with post-translational modifications (PTMs) as neoantigens for autoimmune diabetes.  We use the non-obese diabetic (NOD) mouse model to study the role of proteins with PTMs in the pathogenesis of type 1 diabetes.  Beta cell secretory proteins are subjected to post-translational modifications such as deamidation and di-sulfide bond formation among others.  Such modified proteins/peptides may become neoantigens that can activate endogenous T cells and lead to beta-cell directed autoimmunity.  Ongoing efforts in the lab focus on: (1) temporal correlation between the appearance of humoral immunity to proteins/peptides with PTMs and diabetes development; (2) the role of cellular immunity to proteins/peptides with PTMs in the development of diabetes; (3) the role of endogenous enzymatic pathways for the formation of such neoantigens; (4) the role of neoantigens as a diagnostic tool for autoimmune diabetes; (5) the role of neoantigens for more effective tolerance induction strategies for autoimmune diabetes.

3. Circadian Clock regulation in immune cell function and autoimmune diabetes.  Disruption of circadian rhythms has been linked to inflammatory diseases, however the precise roles of core clock proteins in the function of immune cells have not been elucidated.  Collaborating with the Bass lab, we are investigating the role of BMAL1, one of the core clock proteins, in controlling several fundamental aspects of the immune system. Ongoing efforts in the lab focus on: (1) defining the phenotypic and functional alterations in immune cells caused by disruption of circadian gene regulation; (2) defining the role of circadian gene regulation at the immune cell/beta cell interface and its contribution to the development of autoimmune diabetes; (3) defining the role of circadian gene regulation at the immune cell/transplanted graft interface and its contribution to the development transplant graft rejection.

For more information visit Dr. Luo's faculty profile page

Publications

View Dr. Luo's publications at PubMed

Contact

Email Dr. Luo

Phome 312-908-8147

 Aline Martin Lab

Performing basic and translational research focused on the endocrine regulation of mineral metabolism. Investigation focuses on the relationship between mineral homeostasis, skeleton biology and secretion of the hormone Fibroblast Growth Factor (FGF)-23 by the bone that translates to several acquired and hereditary diseases, such as hypophosphatemic rickets or chronic kidney disease (CKD), in which abnormally elevated production of FGF23 is responsible for various adverse outcomes. 

Her laboratory uses a combination of histology, cell biology, molecular biology and mouse genetics tools to study the bone response to impaired mineral metabolism. The main focus of her research is to understand the bone regulatory mechanisms of FGF23 transcription and cleavage in health and in CKD. The lab currently studies the role of two specific bone factors, PHEX and Dentin Matrix Protein (DMP)-1, which are generally involved in the process of bone mineralization. PHEX and DMP1 mutations lead to hereditary rickets and hypophosphatemia caused by elevated production of FGF23. To date, PHEX and DMP1 contribution to elevated FGF23 production in CKD is unclear and represent a possible therapeutic target for patients with CKD.

Dr. Martin’s laboratory is funded by the National Institute of Health, National Institute of Diabetes and the National institute of Digestive and Kidney Diseases (NIDDK).

Faculty Profile

Aline Martin, PhD

 Rupal Mehta Lab

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

Rupal C Mehta, MD

 Susan Quaggin Lab

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.  

Faculty Profile

Susan Quaggin, MD

 Jason Wertheim Lab

Organ and tissue engineering, 3D scaffold systems, induced pluripotent stem cells, stem and progenitor cell differentiation in 3D matrices, regenerative medicine applications

Research Description

The major area of interest in my laboratory is advancing the state of art in organ regeneration and tissue engineering to develop methods to grow livers and kidneys as a cutting-edge solution to the organ shortage dilemma. Nationally, over 120,000 patients are waiting for solid organ transplantation, yet the number of transplants performed annually falls short of this need by 75%. In the absence of suitable donors for transplantation, organ failure leads to associated health problems, increased health care expenditures and death.  Organ shortage is a national issue with local impact. In 2010 there were just over 1050 solitary kidney, liver, or heart transplants performed in Illinois yet 311 patients died in the state alone, and more than 6650 nation-wide, waiting for an organ.

Our research proposes a multidisciplinary solution to organ shortage by utilizing a tissue engineering approach to rehabilitate the extracellular matrix of organs that are not initially suitable for transplantation. Just-in-time organs, reconstituted with recipient derived progenitor cells, would abrogate the need for long waitlist times and associated waitlist mortality, reduce the reliance on organs from living donors, and obviate the need for immunosuppression. Conceptually, these organs would be prepared from a donor matrix using a recipients own cells at the first signs of organ dysfunction. The re-engineered organ would then be ready for implantation when progressive organ failure indicates the need for transplantation. 

The traditional paradigm in tissue engineering has been to grow cells on synthetic, polymer scaffolds to recreate the organ or tissue of interest. The limitation of this approach is the scale-up. Beyond a critical distance, diffusion of nutrients and oxygen is not sufficient to support cellular life, and a vascular system must be incorporated into the tissue to supply nutrients. It has been technically difficult to design a synthetic micro-vasculature resembling small, terminal capillaries and to combine these structures with functional cells. Our approach challenges this paradigm by using the natural extracellular matrix as a scaffold to support the growth of new cells capable of repopulating the three-dimensional matrix. We have established protocols to remove parenchyma cells from livers and kidneys with a high efficiency of cellular removal and adequate retention of extracellular matrix molecules. We have further repopulated the vasculature of these matrix structures with endothelial cells derived from induced pluripotent stem cell technology. Together, we have partnered with the McCormick School of Engineering at Northwestern University and other leading academic and industrial centers to advance this fast moving field and address the problem of organ shortage.

For more information, visit the faculty profile of Jason Wertheim, MD/PhD or visit the Wertheim Lab website.

Publications

View publications by Jason Wertheim at PubMed

Contact Us

Dr. Wertheim

Lab Phone 312-695-0257

 Myles Wolf Lab

Defining novel mechanisms of disease that can be targeted in randomized trials aimed at improving clinical outcomes among individuals with kidney disease.

Myles Wolf is the Margaret Gray Morton Professor of Medicine and founding Director of the Center for Translational Metabolism and Health within the Institute for Public Health and Medicine at the Feinberg School.

He aims to investigate the role of fibroblast growth factor 23 (FGF23) in disordered mineral metabolism, cardiovascular disease and chronic kidney disease.  His long-term goal is to define novel mechanisms of disease that can be targeted in randomized trials aimed at improving clinical outcomes among individuals with kidney disease. His primary contributions have been in the area of hormonal regulation of phosphate and vitamin D homeostasis, and he has helped to characterize the physiological role of fibroblast growth factor 23 (FGF23) in health and in chronic kidney disease, and the impact of elevated FGF23 levels on adverse clinical outcomes in patients with kidney disease.

During the past decade, Dr. Wolf's research on mineral metabolism has been supported by grants from the American Heart Association, the National Kidney Foundation, the American Society of Nephrology, and the National Institutes of Health. His research has been published in leading general medicine and subspecialty journals including the New England Journal of Medicine, JAMA, the Journal of Clinical Investigation, Circulation, Journal of the American Society of Nephrology, and Kidney International, among others.

Faculty Profile

Myles Wolf, MD, MMSc