Robert A. Star, M.D.

Photo of Robert Star
Scientific Focus Areas: Molecular Pharmacology, Molecular Biology and Biochemistry, Systems Biology, Cell Biology

Professional Experience

  • M.D., Harvard Medical School-MIT, 1980
  • B.A., Harvard University, 1976

Current Research

The morbidity and mortality of acute kidney injury (AKI)—especially sepsis AKI—have remained high, despite numerous attempts at novel therapies. Many agents have worked in animals but failed in clinical trials. Effective treatment likely requires early detection and a better understanding of the pathophysiology of human AKI. Our long-term goals are to find markers to detect AKI and to develop therapies to treat and prevent AKI. We are developing better models that more closely mimic sepsis and sepsis AKI.

Clinically Relevant Sepsis Model of AKI

Sepsis is one of the leading causes of AKI, and 50 percent of patients with sepsis develop AKI. The pathogenesis of sepsis-induced AKI is very poorly understood. There are no drugs to treat sepsis-induced AKI, in part because of the lack of animal models that mimic the human disease. Therefore, we developed several new mouse models based on the cecal ligation and puncture model of polymicrobial sepsis, which has hyperdynamic and hypodynamic phases typical of human sepsis. To make the model realistic, we gave the animals pre-existing conditions (elderly animals or those with chronic kidney disease), and treated the animals with postoperative fluids and antibiotics. The mice developed biochemical and histological renal injury that was similar to human AKI. We are characterizing this model and using it to test treatment strategies.

Select Publications

The role of adenosine 1a receptor signaling on GFR early after the induction of sepsis.
Street JM, Koritzinsky EH, Bellomo TR, Hu X, Yuen PST, Star RA.
Am J Physiol Renal Physiol (2018 May 1) 314:F788-F797. Abstract/Full Text
Antagonism of scavenger receptor CD36 by 5A peptide prevents chronic kidney disease progression in mice independent of blood pressure regulation.
Souza AC, Bocharov AV, Baranova IN, Vishnyakova TG, Huang YG, Wilkins KJ, Hu X, Street JM, Alvarez-Prats A, Mullick AE, Patterson AP, Remaley AT, Eggerman TL, Yuen PS, Star RA.
Kidney Int (2016 Apr) 89:809-22. Abstract/Full Text
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Research in Plain Language

Acute kidney Injury (AKI) leads to high levels of illness and death. In AKI, the kidneys suddenly stop working and no longer remove waste products from the blood. Researchers continue to develop new treatments, however, these have not helped people despite showing promise in tests with animals. We need to detect AKI early to treat it effectively. Scientists need to understand better AKI’s underlying disease processes in people. Our research has several long-term goals. We aim to find markers (biological indicators) to detect AKI. We are also developing therapies to treat and prevent AKI. Our research also generates new tools to study AKI.

Our recent findings suggest a potential therapy for AKI. Many experimental agents can prevent kidney damage in animal models of AKI. However, these must start before the initial injury. Only a few agents can treat AKI. We found that two inflammation fighters inhibit kidney damage in mice with two different kinds of kidney injury. The inflammation-fighting agents are called alpha-melanocyte stimulating hormone (MSH) and interleukin-10 (IL-10). MSH decreases kidney injury, even when given 6 hours after restriction of blood supply (ischemia). IL-10 works when started 1 hour after chemically induced injury. We are now testing an agent that is chemically similar to MSH in studies with people.

Our recent research has also produced an animal model that mimics sepsis. Sepsis occurs when inflammation takes over the entire body. Sepsis is one of the leading causes of AKI. Half of patients with sepsis develop AKI. Scientists understand very little about how sepsis leads to AKI. There are no drugs to treat sepsis-induced AKI. Researchers might improve the situation with animal models that mimic the human disease. Therefore, we developed a new mouse model. This model features phases typically seen in human sepsis. The model is similar in biochemistry and histology to human AKI. We are now describing this model. We are also testing treatment strategies with this model. Our tests have determined that several agents are effective, even when started 6 to 12 hours after sepsis begins.