Leppert Lab in the department of urology

Current Projects

Our research aims to answer several questions:

    Translational Research

  1. Nanofluidic Proteomic Immunoassays in Renal Cell Carcinoma Diagnosis and Treatment Response:
    Renal cell carcinoma represents a clinical challenge as it is a heterogeneous disease with several distinct tumor types, including clear cell, papillary, chromophobe, collecting duct, and unclassified. Each subtype demonstrates unique clinical behavior and responds to different treatments. Given this heterogeneity, there is a need for accurate molecular markers that can guide individual treatment decisions beyond the limits of current staging systems. To assess oncoproteins and their phosphorylation state in clinical specimens in clinical specimens, we are applying a novel nano-immunoassay (NIA) technology that incorporates isoelectric focusing of proteins, followed by antibody detection of specific epitopes with chemiluminescence to the diagnosis of RCC. NIA profiles may also demonstrate signatures of response, or resistance to, targeted therapeutics in advanced RCC.

  2. IQGAP1 Renal Cell Carcinoma:
    IQ motif-containing GTPase-activating protein 1 (IQGAP1) is a scaffold protein that is expressed in many human tissues. IQGAP1 is known to bind with more than 90 proteins and protein complexes, including VEGFR2, MEK, and ERK. Mice lacking IQGAP1 demonstrate a normal phenotype and remain fertile. Dr. Khavari (Nature Medicine, 2013) demonstrated the role of IQGAP1 in RAS-driven skin cancers, that depletion of IQGAP1 reduced ERK activation, and that interfering with IQGAP1-ERK binding using a “WW” peptide inhibited tumorigenesis. IQGAP1 mRNA is strongly expressed in human renal tissue. Like many cancers, RCC also is known to overexpress phosphorylated ERK protein. The interaction of IQGAP1 with ERK and other relevant kinases suggests that it is well positioned to combat adaptive resistance to TKIs and support its role as both a potential primary and combination therapeutic approach in RCC. However, the role of IQGAP1 in modulating the RAS pathway in RCC has not been studied. Taken together, these data suggest that IQGAP1 holds promise as a novel diagnostic and prognostic biomarker, as well as a potential new therapeutic target in RCC.

  3. Epidemiology and Health Services Research

  4. Renal Morbidity Following Kidney Cancer Surgery:
    We are interested in determining the impact of significant loss of renal mass resultant from kidney cancer surgery. Large clinical studies demonstrate that loss of kidney function correlates with an increased incidence of hospitalizations, cardiovascular events, and all-cause mortality. Patients with renal cell carcinoma (RCC) tend to be older, often have co-morbid conditions associated with lower baseline kidney function, and may be particularly sensitive to further loss of kidney function following kidney cancer surgery. Hence, there is a great need to determine the comparative effectiveness of alternative surgical approaches for RCC on kidney function and downstream clinical outcomes. To address this need, we are working to establish an electronic data registry of persons that underwent kidney cancer surgery within the Veterans Affairs (VA) health care system, 2) characterize the change of kidney function due to specific types of kidney cancer surgery, and 3) to correlate the type of kidney cancer surgery received and post-operative kidney function with the risk of ESRD, conditions associated with CKD, cardiovascular events, hospitalizations, and all-cause mortality among RCC patients in the VA health care system. Ultimately, comparing these surgical strategies can provide opportunities to improve care for patients diagnosed with RCC.

  5. Personalized Life Expectancy to Encourage High Value Prostate Cancer Care:
    Veterans receiving care in the Veterans Health Administration may have higher prostate cancer risk due to a family history, race, or exposure to toxins such as Agent Orange and burn pits. Prostate cancer is the most common male cancer, presents in older men that may have additional medical conditions, and often follows an indolent course. It is estimated that 60% of all prostate cancer cases represent an “overdiagnosis” of clinically insignificant tumors. For prostate cancer patients, “overdiagnosis” refers to the diagnosis of a disease process that would otherwise not go on to cause symptoms or death. Similarly, “overtreatment” refers to the treatment of prostate cancers that would not otherwise go on to cause symptoms or death. Our objective is to leverage the power of the standardized electronic health record in the VHA to generate personalized risk-adjusted life expectancy estimates. We will use these estimates to provide critical information to inform prostate cancer screening and treatment medical decision-making. These efforts have the potential to deliver higher quality prostate cancer care, by treating patients most likely to benefit, and while avoiding futile treatment and minimizing treatment-related side effects.

Funding Sources

Work described in these projects is supported by one or more of the following funding sponsors:

  • The Department of Defense
  • The VA Health Services Research and Development
  • National Cancer Institute, NIH
  • The NIDDK, NIH
  • The Stanford Cancer Institute
  • The Translational Research and Applied Medicine Program at Stanford University
  • The Department of Urology at Stanford University

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