Ryan C. Henrici, MD, PhD

Associate Scholar

  •  Lecturer| University of Pennsylvania
  •  United Kingdom of Great Britain and Northern Ireland | Uganda
  •   Capacity-building | Infectious disease | Malaria | Sickle Cell Disease

Languages: English (native), French (working proficiency)

Bio statement

Neglected diseases affect millions of people each year, inflicting enormous public health and economic cost to developing nations. In many cases, antimicrobial drug resistance and non-communicable comorbidities multiply these costs and complicate global efforts to improve child and adult health. I work at the intersections of biology, drug development, and clinical medicine with a special focus on malaria and Sickle Cell Disease. These diseases are pathophysiologically intertwined and disproportionately affect patients in tropical settings, causing considerable morbidity and mortality.

In particular, I map the cellular mechanisms of malarial development and drug resistance, track the evolution of drug resistance in the field, and study the consequences of malarial infection and outcomes of treatment in children with SCD. I also work closely with biopharmaceutical partners to build and test new drugs for the treatment of infections, including malaria, and sickle cell disease, with an emphasis on equitable drug development

Recent global health projects

I recently completed a major project to measure the impacts of key mutations in the malaria parasite genome on drug resistance using the CRISPR-Cas9 system and develop new antimicrobial agents. By understanding the "power" of specific mutations to cause resistance, we may better track the evolution and spread of drug resistance across the tropics. In particular, we determined that the primary mechanism of resistance to frontline artemisinin compounds involves manipulations of haemoglobin uptake and digestion.

Separately, my colleagues at Indiana University and I noticed that children with Sickle Cell Disease and acute malaria may not be adequately treated with artemisinins. Connecting this observation to my prior work, it is possible that HbSS haemoglobin may be a poor substrate for artemisinin activation and antimalarial activity. The stakes of ineffective antimalarial therapy for children with SCD are high. In partnership with Makerere University, we are undertaking the first controlled study of antimalarial efficacy in children with SCD.

Broadly, I collaborate with colleagues across Sub-Saharan African and Southeast Asia to understand the biology of the malaria parasite and SCD and build local research capacity.

Selected publications

Henrici RC, Sautter CL, Bond C, Opoka RO, Namazzi R, Datta D, Ware RE, Conroy AL, John CC. Decreased parasite burden and altered host response in children with sickle cell anemia and severe anemia with malaria. Blood Adv. 2021 Nov 23; 5(22): 4710-4720.

Henrici RC, Edwards RL, Zoltner M, van Schalkwyk DA, Hart MN, Mohring F, Moon RW, Nofal SD, Patel A, Flueck C, Baker DA, Odom John AR, Field MC, Sutherland CJ. The Plasmodium falciparum Artemisinin Susceptibility-Associated AP-2 Adaptin µ subunit is Clathrin Independent and Essential for Schizont Maturation. mBio. 2020 Feb 25; 11(1):e02918-19

Henrici RC, van Schalkwyk DA, Sutherland CJ. Transient temperature fluctuations severely decrease P. falciparum susceptibility to artemisinin in vitro. Int J Parasitol Drugs Drug Resist. 2018 Dec 1;9:23-26. doi:10.1016/j.ijpddr.2018.12.003

Henrici RC, Sutherland CJ. Alternative pathway to reduced artemisinin susceptibility in Plasmodium falciparum. Proc Natl Acad Sci U S A. 2018 Dec 11;115(50):12556-12558. doi: 10.1073/pnas.1818287115.