Department of Medicine

Research

Nephrology Research

Translational research in transplantation is a major focus of our research efforts. We have resolved signaling requirements of T cells, mechanisms of action of immunosuppressive drugs, mechanisms of post-transplant malignancy, and developed molecular assays for assessing transplant status. We have demonstrated that T cell CD2 antigen is a signaling receptor for antigen presenting cells, and resolved a T cell co-stimulation pathway of importance to transplantation (reported in J Exp Med 1990). We discovered a novel mechanism for cancer metastasis (Nature 1999) and identified new treatments that preserve transplant function while blocking tumor progression (Transplantation 2002 and Kidney International 2003). We have developed noninvasive and nucleic acid based assays for the prediction of transplant status and outcome (NEJM 2001 and NEJM 2005). We have contributed to the first ever induction of tolerance to HLA-mismatched kidney transplants (reported in NEJM 2008). Our research in type one diabetes has resulted in the first successful human pancreatic islet transplantation in the tri-state area, and in a curative cell therapy for type one diabetes (Proc Natl Acad Sci USA 2007).

Transplantation Laboratory

The Transplantation Laboratory, within the Division of Nephrology and Hypertension, has made substantive contributions in the areas of transplant immunology and molecular biology, and has resolved mechanisms of action of immunosuppressive drugs, signaling requirements of T cells, mechanisms of post transplant malignancy, and molecular diagnostics. We are refining gene expression profiles to accurately predict organ transplant status. In our recent studies, we have found that the two major complications affecting all organ transplants, acute rejection and chronic rejection, can be predicted with greater than 95% accuracy with the use of the gene expression panel developed in our laboratory (reported NEJM 2001 and NEJM 2005). One of our major goals is to use the gene expression profiles of transplant patients to reduce drug therapy and minimize or eliminate drug related complications such as life threatening infections or malignancy. Our gene profiling studies should pave the way for the safe induction of transplantation tolerance. In this regard, our molecular studies have already contributed to the first ever induction of tolerance to HLA-mismatched kidney transplants (reported in NEJM 2008).

Diabetes Research Laboratory

The Diabetes Research Laboratory includes the Human Islet Isolation Center, responsible for the first successful human islet transplantation in the tri-state area. In 2007, we developed a new type of cell therapy, in collaboration with Dr. R. M. Steinman of Rockefeller University, that may cure type one diabetes, as well as protect the transplanted islets from autoimmune destruction characteristic of type one diabetes (reported in Proc Natl Acad Sci USA 2007). We have also developed a novel protocol to improve the function of transplanted islets (reported in the Journal of the American Society of Nephrology 18: 213-22, 2007).

There are two major challenges to widespread use of islet transplantation in type one diabetic patients. They are: the need for lifelong immunosuppressive therapy, and the need for a large islet mass (usually islets from 2 pancreata are required to make a patient insulin-independent). In collaboration with Dr. R.G. Crystal (Chief of the Division of Pulmonary and Critical Care Medicine in the Department of Medicine at Weill Cornell Medicine), we have developed a systemic transforming growth factor beta1 gene therapy that obviates the need for immunosuppressive therapy to protect islet grafts. In collaboration with Dr. K. Manova (MSKCC), we have developed methods to accurately assess islet status using confocal laser microscopy. Importantly, we demonstrated that systemic transforming growth factor beta1 gene therapy can restore self tolerance and facilitate regeneration of beta cell function in a stringent mouse model of type 1 diabetes (Luo et al. Transplantation 2005).

The current barriers to successful clinical islet transplantation include the need for life long immunosuppressive therapy and the need for a large islet mass. Our research discoveries hold considerable promise for overcoming these barriers. Our research results from NIH and JDRF sponsored studies of islet transplantation have been presented at the following National Meetings: American Society of Nephrology 2006, American Transplant Congress 2007, and American Diabetes Association 2007.

Choi Laboratory

Dr. Mary Choi

Mary Choi, M.D.

Principal Investigator: Mary E. Choi, M.D.

Research Interests: Molecular and cellular mechanisms of tissue injury and fibrosis, TGF-β1, cell signaling pathways in the kidney

Research in the Choi laboratory centers on understanding the cellular and molecular mechanisms of tissue inflammation and injury, including the kidney, lung, and vasculature, in the pathogenesis of acute and chronic diseases. Our work has focused on examining the mechanisms of signal transduction by Transforming Growth Factor-beta1 (TGF-β1), a pleiotropic cytokine and key mediator of tissue injury response and kidney fibrosis. We have extensively examined how TGF-β1 effects are mediated by the distinct TGF-β receptors via activation of intracellular signaling molecules downstream to the receptors in a cell-specific manner to regulate cellular responses in renal cells. Investigations in the laboratory have included (1) cloning and characterization of the cell surface receptors, and identification of novel interacting proteins that are involved in TGF-β1 signal transduction, (2) delineating the downstream intracellular signal transducing pathways that mediate TGF-β1 signals, in particular, the role of the mitogen-activated protein kinase (MAPK) pathways, and (3) the cellular and molecular regulation of TGF-β1 induction of cytoprotectants, such as heme oxygenase-1 (HO-1) and carbon monoxide (CO). We are currently investigating novel mechanisms of regulation and function of autophagy, inflammasomes and necroptosis in models of organ injury, including the kidney, lung and heart. In collaboration with Dr. Augustine Choi (Professor, Division of Pulmonary & Critical Care Medicine), Dr. Jeffrey Laurence (Professor of Medicine, Division of Hematology & Medical Oncology), and Dr. Oleh Akchurin (Assistant Professor of Pediatrics, Division of Pediatric Nephrology), we are also studying mechanisms of sepsis, acute and chronic lung injury, HIV/antiretroviral therapy related cardiac/kidney fibrosis, and juvenile chronic kidney disease. The ultimate goal of our research is to identify novel therapeutic targets that will provide cytoprotection against tissue injury in progressive kidney diseases. Our research is supported by the following grants from the NIH.

Title: TGF-beta signaling in the kidney
Sponsor: NIH R01 DK057661
Principal investigator: M. Choi

Title: Heme Oxygenase-1/Carbon Monoxide in Sepsis
Sponsor: NIH R01 HL079904
Principal investigator: M. Choi

Title: Heme Oxygenase-1/Carbon Monoxide in lung vascular injury
Sponsor: NIH R01 HL060234
Principal Investigator: M. Choi/A. Choi (MPI)

Title: Cytoprotection by Carbon Monoxide in sepsis and acute lung injury
Sponsor: NIH P01 HL108801
Principal Investigator: M. Perrella
Co-Investigator (Project 1): M. Choi

Title: Mechanisms of HIV/ART related cardiac fibrosis
Sponsor: NIH R21 HL125044-01
Principal Investigator: J. Laurence
Co-Investigator: M. Choi

Title: Distinct and Overlapping Pathways of Fibrosis and Emphysema in Cigarette Smokers
Sponsor: NIH P01 HL114501-03
Principal Investigator: A. Choi
Co-Investigator: M. Choi

Title: Inflammasomes: Regulation and Function in Acute Lung Injury
Sponsor: NIH R01 HL055330
Principal Investigator: A. Choi
Co-Investigator: M. Choi

Title: Growth delay and inflammation in juvenile chronic kidney disease
Sponsor: NIH 5UL1 R000457-09
Principal Investigator: O. Akchurin
Co-Investigator: M. Choi

Research Studies

The Division of Nephrology and Hypertension has ongoing studies that are actively enrolling for recruitment. Our innovative research has enabled us to develop and better understand diseases affecting the kidney and renal systems, and alternative non-invasive ways to detect allograft dysfunction. Under the direction of Dr. Manikkam Suthanthiran, the division continues to grow and expand its research, and make significant scientific contributions to the medical world.

We participate in research studies involving the following conditions/diseases:

  • Cardiovascular/Heart
  • Hypertension/High Blood Pressure
  • Kidney/Renal Disease
  • Healthy Volunteers

More information can be found on the JCTO website. For additional clinical trial studies under the Division of Nephrology and Hypertension, please visit The Rogosin Institute.

Closed to Enrollment/Retrospective Chart Reviews

Hypertension Treatment Assessment and Quality Assurance and Research

  • Sponsor: Internal Funding (WCMC)
  • Disease Status and/or Stage: Hypertension
  • PI: Dr. August

A Multicenter, Phase 2, Open-Label, Controlled, Extension Study for Stage 1 SUBJECTS of Study A3921009 to Evaluate the Long-Term Safety and Efficacy of CP-690,550 versus Tacrolimus, When Co-Administered with Mycophenolate Mofetil in Renal Allograft Recipients

  • Sponsor: Pfizer Pharmaceuticals
  • Disease Status and/or Stage: Kidney Transplant Recipients
  • PI: Dr. Dadhania

Characterization of Immune Function in Transplant Recipients

  • Sponsor: Internal Funding (WCMC)
  • Disease Status and/or Stage: Kidney Transplant Recipients
  • PI: Dr. Dadhania

Correlation of Donor Proinflammatory mRNA Profiles with Early Outcomes of Thoracic and Abdominal Transplantation-CTOT 3

  • Sponsor: NIH; Qatar National Research Foundation (QNRF)
  • Disease Status and/or Stage: Organ Transplant Recipients
  • PI: Dr. Dadhania

Renal Transplantation for Patients with End Stage Renal Disease and ABO Incompatible Donors

  • Sponsor: Internal Funding (WCMC)
  • Disease Status and/or Stage: Kidney Transplant Recipients
  • PI: Dr. Dadhania

The Impact of PCP Prophylaxis on Renal Transplantation

  • Sponsor: Internal Funding (WCMC)
  • Disease Status and/or Stage: Kidney Transplant Recipients
  • PI: Dr. Lee

The Impact of Vitamin D Status on Renal Transplant Outcomes

  • Sponsor: Internal Funding (WCMC)
  • Disease Status and/or Stage: Kidney Transplant Recipients
  • PI: Dr. Lee

Nebivolol versus Metoprolol: Comparative Effects on Fatigue and Quality of Life (QOL)

  • Sponsor: Forest Research Institute, Inc.
  • Disease Status and/or Stage: Hypertension
  • PI: Dr. Mann

A Multi-center Study of Prevalence and Potential Contributors to Burnout Among Resident Physicians starting in Medicine in 2011-2012

  • Sponsor: Mt. Sinai
  • Disease Status and/or Stage: Healthy Resident Physicians
  • PI: Dr. Pecker

Cytokine Levels in Hypertensive and Normotensive Individuals

  • Sponsor: Internal Funding (WCMC)
  • Disease Status and/or Stage: Hypertension; Healthy Volunteers
  • PI: Dr. Suthanthiran

TGF-beta and the Progression of Renal Disease

  • Sponsor: Internal Funding (WCMC)
  • Disease Status and/or Stage: Renal Disease
  • PI: Dr. Suthanthiran

TGF-beta and Excess Renal Disease in African Americans

  • Sponsor: Internal Funding (WCMC)
  • Disease Status and/or Stage: Renal Disease
  • PI: Dr. Suthanthiran

Collaborative Research Studies with Division of Transplant Surgery

Thymoglobulin Induction Therapy with Minimal Immunosuppression and Evaluation of Allograft Status by Biopsy and mRNA Profiles (TIMELY II)

  • Study Status: Open to Enrollment
  • Sponsor: NIH; Qatar National Research Foundation (QNRF); Genzyme Corporation
  • Disease Status and/or Stage: Kidney Transplant Recipients
  • PI: Dr. Kapur

mRNA and microRNA Profiles in Renal Transplant at the Time of Organ Reperfusion

  • Study Status: Open to Enrollment
  • Sponsor: Qatar National Research Foundation (QNRF)
  • Disease Status and/or Stage: Kidney Transplant Recipients
  • PI: Dr. Kim

Contact Information

Nephrology and Hypertension

Manikkam Suthanthiran, M.D., Chief

ThuTrang Du, Administrator
Room: A-569
Tel: (212) 746-4430
Fax: (212) 746-6894
tdu@med.cornell.edu

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