Sunder Sims-Lucas is a basic research scientist whose focus is on the formation of the developing vasculature in the kidney and the predisposition to adult-onset disease when there is defective development. He is involved in a major initiative by the NIH in the growth of new kidney tissues. His laboratory also studies blood flow and hypoxia and the role they play in patterning the various renal lineages. He recently began exploring the role of the microvasculature in acute kidney injury. He has authored more than 45 publications and, despite being an early-stage investigator, has been supported by many NIH and DoD grants, including a K01, an R03, and U24 grants. He has acquired local awards, including a Children’s Hospital of Pittsburgh Research Advisory Committee grant, a University of Pittsburgh Vascular Medicine Institute pilot award, and a University of Pittsburgh McGowan Institute for Regenerative Medicine pilot award.
Current Lab Projects
Acute kidney injury
Acute kidney injury (AKI) occurs in nearly 1 of 5 hospitalized patients and is associated with increased morbidity and mortality across all ages. Many AKI patients will recover kidney function post-injury but then progress to chronic kidney disease (CKD). The mechanisms are poorly understood and there are currently no effective therapies to prevent, limit, or reverse the tissue damage. There is a critical need to identify mechanisms involved in the pathogenesis of AKI. Our long-term goal is to elucidate these mechanisms and leverage them for new therapies to limit AKI and prevent the transition to CKD. We have two major projects that are currently be investigated: 1. Sirtuin 5 mediated protection against AKI and 2. Mir17~92 in the renal endothelium during AKI. We are in the process of designing pre-clinical studies to test whether both these mechanisms can be leveraged to protect against AKI.
Maternal environment and kidney formation
The maternal environment is critical to not only the health of the fetus but also the health and development of the kidney. Alterations in the maternal environment can lead to drastic changes in the development of the kidney and lead to congenital kidney abnormalities. We have two major projects that are currently be investigated: 1. The role of maternal diabetes on kidney formation and 2. Low protein diet and kidney formation.
Renal Microvasculature and blood flow
Formation of the vasculature is a critical developmental process that requires tightly regulated cellular and molecular processes. The developing kidney is a very vascular organ that receives approximately 20% of the total cardiac output. The peritubular capillaries surround the nephron tubules and play a critical role in reabsorption and electrolyte balance. Little is known about the various origins of the peritubular capillary network and the role of the peritubular capillaries in normal development and also during disease processes. His laboratory identified an endothelial progenitor in the kidney that is critical for kidney development and also limiting postnatal injury. Dr. Sims-Lucas’ robust program also interrogates the role of oxygenation and blood flow in patterning the formation of the kidney.
VHL mutations and kidney cancer
VHL (the major regulator of HIFs) is a tumor suppressor protein, which is a protein upon mutation causes tumorigenesis and cancer development, with the kidney as one of the primary sites. Loss of VHL plays a prominent role in the pathogenesis of clear cell renal cell carcinoma (ccRCC), and up to 70% of all ccRCC cases are attributed to VHL gene defects. We have two major projects that are currently be investigated: 1. The role of VHL in driving nephron progenitor differentiation and 2. The development of ccRCC cancer models.