Major Areas of Research
- Mechanisms by which globins regulate signaling between endothelial cells and vascular smooth muscle cells in human resistance arteries
- The impact of genetic variation in globin genes on vascular function and vascular disease risk
- Nitric oxide metabolism and endothelial function in malaria and sickle cell disease
The Physiology Unit studies the mechanisms by which endothelial alpha globin regulates signaling between endothelial cells and vascular smooth muscle cells in human resistance arteries. We seek to understand how common structural variants in the human alpha globin gene loci affect expression of alpha globin in the vascular endothelium, alter the arterial response to vasoactive stimuli, and modify susceptibility to vascular complications of chronic and infectious diseases. These lines of investigation offer an opportunity to explore the long-held observations that alpha globin gene deletions reduce the severity of malaria infection and delay or prevent the vascular complications of sickle cell anemia. By understanding how alpha globin regulates cell-cell signaling in the vessel wall, we may be able to develop new strategies to modulate human endothelial function and treat or prevent diseases at the vascular endothelium.
We integrate human clinical investigations with experiments conducted in model systems. We use population-based studies to test hypotheses generated in the lab and clinic. Our work is carried out in the NIH Clinical Center, in laboratories on the NIH campus, and with collaborators in the United States and abroad.
Dr. Ackerman received his D. Phil. from the University of Oxford where he studied variation in cytokines genes with Dominic Kwiatkowski. He earned a medical degree from Harvard Medical School and completed an internship and residency in internal medicine at Massachusetts General Hospital. In 2007, he came to the NIH Clinical Center as a clinical fellow and went on to become board certified in internal medicine and critical care medicine. In 2011, he was awarded a spot in the NIAID Transition Program in Clinical Research to study the metabolic determinants of nitric oxide signaling and endothelial dysfunction in severe malaria. He began his tenure-track work on endothelial alpha globin in the NHLBI sickle cell branch in 2014. He moved to the NIAID Laboratory of Malaria and Vector Research in 2017 to expand his clinical research program at the NIH Clinical Center and to engage with NIAID’s International Centers for Excellence in Research.
Dr. Ackerman was named an NIH-Lasker clinical research scholar in 2014. He received NIAID’s mentor of the year award in 2014 and the NHLBI director’s learning environment award in 2017.
Dr. Ackerman has mentored students and fellows at all levels of training. He seeks to provide opportunities for individuals from backgrounds that have previously been underrepresented in science by mentoring trainees in the NIH Academy Enrichment Program and the Intramural NIAID Research Opportunity program. He serves as an advisor in the NIH’s Medical Research Scholars Program and on the selection committee for the Malaria Research Program’s collaborative fellowship.
Inquiries about predoctoral and postdoctoral fellowships, as well as Ph.D. studentships, in the NIH Graduate Partnership Program are welcome.
A. Parker Ruhl, M.D., M.H.S.
Xianke Zeng, M.D., Ph.D.
Mary Jackson, RN
Steven Brooks, Ph.D.
Aline da Silva Moreira, Ph.D., M.S.
Ackerman H, Ayestaran A, Olola CHO, Jallow M, Agbenyega T, Bojang K, Roberts DJ, Krishna S, Kremsner PG, Newton CR, Taylor T, Valim C, Casals-Pascual C. The effect of blood transfusion on outcomes among African children admitted to hospital with Plasmodium falciparum malaria: a prospective, multicentre observational study. Lancet Haematol. 2020 Nov;7(11):e789-e797.
Alkaitis MS, Wang H, Ikeda AK, Rowley CA, MacCormick IJ, Chertow JH, Billker O, Suffredini AF, Roberts DJ, Taylor TE, Seydel KB, Ackerman HC. Decreased Rate of Plasma Arginine Appearance in Murine Malaria May Explain Hypoargininemia in Children With Cerebral Malaria. J Infect Dis. 2016 Dec;214(12):1840-1849.
Pecker L.H., Ackerman H.C. (2016) Cardiovascular Adaptations to Anemia and the Vascular Endothelium in Sickle Cell Disease Pathophysiology. In: Costa F., Conran N. (eds) Sickle Cell Anemia. Springer, Cham. https://doi.org/10.1007/978-3-319-06713-1_7
Chertow JH, Alkaitis MS, Nardone G, Ikeda AK, Cunnington AJ, Okebe J, Ebonyi AO, Njie M, Correa S, Jayasooriya S, Casals-Pascual C, Billker O, Conway DJ, Walther M, Ackerman H. Plasmodium Infection Is Associated with Impaired Hepatic Dimethylarginine Dimethylaminohydrolase Activity and Disruption of Nitric Oxide Synthase Inhibitor/Substrate Homeostasis. PLoS Pathog. 2015 Sep;11(9):e1005119.
Rowley CA, Ikeda AK, Seidel M, Anaebere TC, Antalek MD, Seamon C, Conrey AK, Mendelsohn L, Nichols J, Gorbach AM, Kato GJ, Ackerman H. Microvascular oxygen consumption during sickle cell pain crisis. Blood. 2014 May 15;123(20):3101-4.
Miller LH, Ackerman HC, Su XZ, Wellems TE. Malaria biology and disease pathogenesis: insights for new treatments. Nat Med. 2013 Feb;19(2):156-67.