• U.S. Department of Health & Human Services
• National Institutes of Health      

• Contact Us
• Get Email Alerts
• Font Size      

Gregory J. Kato, M.D.

Sickle Cell Vascular Disease Section

Background

Gregory Kato is the Director of and an Investigator in the Sickle Cell Vascular Disease Section of the NHLBI's Pulmonary and Vascular Medicine Branch. He graduated from the George Washington University School of Medicine and Health Sciences in 1985. He completed a residency in pediatrics at Children’s Hospital of Los Angeles and a fellowship in pediatric hematology-oncology at the Johns Hopkins Children’s Center. Dr. Kato joined the NIH in 2003 and has been a tenure-track Investigator since 2008. He has received numerous awards and honors for his work at NIH and elsewhere, including a Young Investigator Award from the American Society of Clinical Oncology (1991), a Clinician Scientist Award from Johns Hopkins University School of Medicine (1998), and an NHLBI Merit Award (2008). Dr. Kato currently serves as part-time faculty at the Johns Hopkins University School of Medicine. His clinical areas of expertise include sickle cell disease (adult and pediatric), pulmonary hypertension, and vasculopathy.

Research Interests

Sickle cell disease (SCD) is a genetic blood disorder caused by a mutation in the hemoglobin gene, characterized by the abnormal, rigid, sickle shape of red blood cells. Dr. Kato has both a clinical and an active translational research interest in the disorder. His work focuses on associated diseases of the blood vessel wall, particularly pulmonary hypertension, which is linked to early mortality in these patients. Research from his group and others has strongly suggested that pulmonary hypertension constitutes part of a syndrome of sickle cell vasculopathy that also includes cutaneous leg ulceration and priapism (a painful, persistent penile erection). Ongoing research is investigating whether chronic renal disease, ischemic stroke, and other chronic complications of sickle cell disease might also be consequences of sickle cell vasculopathy.

Dr. Kato has been integral in developing a scientific model to explain the development of sickle cell vasculopathy. In addition to their propensity to occlude capillaries, sickle cells are also prone to prematurely break down in a process called hemolysis. The breakdown products of blood cells appear to be a signficant cause of vascular dysfunction.
Dr. Kato is currently studying the multifactorial mechanisms that link hemolysis with pulmonary hypertension by combining blood flow physiology studies, clinical trials, and proteomic analysis of plasma. His group and others have shown a link between pulmonary hypertension and elevated levels of placental growth factor (PGF), a member of the vascular endothelial growth factor (VEGF) family. Dr. Kato is investigating the hypothesis that iron overload after hemolysis causes the increase in PGF production, which in turn produces elevated levels of endothelin-1, a mediator of vascular tone.

Hemolysis also affects levels of nitric oxide—another regulator of blood vessel health—through multiple pathways. Hemoglobin released into blood plasma from red blood cells directly inactivates nitric oxide. Arginase is also released from hemolyzed red cells into blood plasma. Arginase depletes levels of the amino acid L-arginine, the required substrate for nitric oxide production by the nitric oxide synthase family of enzymes. In this way, hemolysis both reduces nitric oxide production and accelerates its destruction.

To optimize clinical studies that establish the relationship between plasma hemoglobin and pulmonary hypertension, Dr. Kato has been investigating biomarkers such as exhaled carbon monoxide (CO), which results from an enzymatic reaction by which a single molecule of CO is released for every molecule of heme produced in the breakdown of blood cells.

In addition, two therapeutic trials are currently in progress:

1. Topical sodium nitrite for leg ulcers for patients with sickle cell disease
2. AES-103, a potential anti-sickling drug

Although the focus of Dr. Kato’s research is firmly on sickle cell disease, he sees important parallels between pulmonary hypertension in SCD and in the overall population. Pulmonary hypertension in SCD does not have a single cause, but is related to additive risk factors not limited to hemolytic breakdown, including triglyceride levels and age. Many of those risk factors, and hence mechanisms, are shared with the development of atherosclerosis in the general population, meaning that research in both areas may have bidirectional impact.

Selected Publications

Infrared imaging of nitric oxide-mediated blood flow in human sickle cell disease.
Gorbach AM, Ackerman HC, Liu WM, Meyer JM, Littel PL, Seamon C, Footman E, Chi A, Zorca S, Krajewski ML, Cuttica MJ, Machado RF, Cannon, Kato GJ.
Microvasc. Res. 2012 Nov;84(3):262-9.
[Text Abstract on PubMed]

Atorvastatin reduces serum cholesterol and triglycerides with limited improvement in vascular function in adults with sickle cell anemia.
Bereal-Williams C, Machado RF, McGowan, Chi A, Hunter CJ, Kato GJ.
Haematologica. 2012 Nov;97(11):1768-70.
[Text Abstract on PubMed]

Mortality in adults with sickle cell disease and pulmonary hypertension.
Mehari A, Gladwin MT, Tian X, Machado RF, Kato GJ.
JAMA. 2012 Mar 28;307(12):1254-6.
[Text Abstract on PubMed]

High levels of placenta growth factor in sickle cell disease promote pulmonary hypertension.
Sundaram N, Tailor A, Mendelsohn L, Wansapura J, Wang X, Higashimoto T, Pauciulo MW, Gottliebson W, Kalra VK, Nichols WC, Kato GJ, Malik P.
Blood. 2010 Jul 8;116(1):109-12.
[Text Abstract on PubMed]

Proteomic identification of altered apolipoprotein patterns in pulmonary hypertension and vasculopathy of sickle cell disease.
Yuditskaya S, Tumblin A, Hoehn GT, Wang G, Drake SK, Xu X, Ying S, Chi AH, Remaley AT, Shen RF, Munson PJ, Suffredini AF, Kato GJ.
Blood. 2009 Jan 29;113(5):1122-8.
[Text Abstract on PubMed]

Gregory J. Kato's Full List of Publications