Description of Research Expertise

My expertise is in rare disorders that affect LDL and HDL cholesterol metabolism. My research interest is focused in understanding the cause of these conditions, finding novel ways to treat them, and ultimately improve their clinical management. 

Currently, I have two active areas of research in rare disorders affecting LDL and HDL metabolism:

Homozygous Familial Hypercholesterolemia or HoFH - HoFH is the rarest form of Familial Hypercholesterolemia (FH) and affects approximately 1 in every ~350,000 people. Untreated LDL cholesterol levels are usually >400 mg/dL, and if left untreated, are associated with premature cardiovascular disease as early as childhood. Patients with HoFH respond insufficiently to conventional lipid lowering drugs, such statins. Penn has a longstanding research program dedicated to the development of novel treatment options for HoFH, spanning from gene therapy to the development of lomitapide and, more recently, evinacumab.

LCAT deficiency – Lecithin:cholesterol acyl transferase (LCAT) is an enzyme involved in cholesterol metabolism. It esterifies the cholesterol carried by HDL and LDL. Familial LCAT deficiency (FLD) and fish-eye disease (FED) are two very rare disorders caused by LCAT deficiency. Both disorders are associated with very low HDL levels and corneal opacities. Additionally, patients with FLD develop renal disease early in life that often quickly progresses to renal failure requiring dialysis or transplant.
If you would like to learn more about these diseases or are interested in collaborating in my research, you can contact me at: mcuchel@pennmedicine.upenn.edu.

Ongoing Clinical Research Programs:
CASCADE FH Registry (NCT01960244): A longitudinal observational registry for patients diagnosed with FH.
HICC registry (NCT04815005): An international registry specifically dedicated to collecting data on HoFH.
LCAT-D registry (NCT06217588): An international registry specifically dedicated to collecting data on LCAT deficiency.

Selected Publications

Cuchel M, Bajaj A.: Type 2 diabetes in familial hypercholesterolaemia: another look at traditional risk factors Lancet Diabetes Endocrinol : 2024.

Reijman MD, Tromp TR, Hutten BA, Hovingh GK, Blom DJ, Catapano AL, Cuchel M, Dann EJ, Gallo A, Hudgins LC, Raal FJ, Ray KK, Sadiq F, Soran H, Groothoff JW, Wiegman A, Kusters DM; Homozygous Familial Hypercholesterolaemia International Clinical Collaborators (HICC); Children with Homozygous Hypercholesterolemia on Lipoprotein Apheresis: an International Registry (CHAIN) consortia.: Cardiovascular outcomes in patients with homozygous familial hypercholesterolaemia on lipoprotein apheresis initiated during childhood: long-term follow-up of an international cohort from two registries Lancet Child Adolesc Health 8 (7): 491-499,2024.

Gidding SS, Ballantyne CM, Cuchel M, de Ferranti S, Hudgins L, Jamison A, McGowan MP, Peterson AL, Steiner RD, Uveges MK, Wang Y.: It is Time to Screen for Homozygous Familial Hypercholesterolemia in the United States Glob Heart 19 : 43,2024.

Alfaro G, Pendyala J, Sulewski M, Miller M, Vitali C, Cuchel M.: Longitudinal analysis of clinical and laboratory biomarkers in a patient with familial lecithin: Cholesterol acyltransferase deficiency (FLD) and accelerated eGFR decline: A case study J Clin Lipidol : 2024.

Mulder JWCM, Tromp TR, Al-Khnifsawi M, Blom DJ, Chlebus K, Cuchel M, D'Erasmo L, Gallo A, Hovingh GK, Kim NT, Long J, Raal FJ, Schonck WAM, Soran H, Truong TH, Boersma E, Roeters van Lennep JE; Homozygous Familial Hypercholesterolemia International Clinical Collaborators.: Sex Differences in Diagnosis, Treatment, and Cardiovascular Outcomes in Homozygous Familial Hypercholesterolemia JAMA Cardiol : doi: 10.1001/jamacardio.2023.5597,2024.

CureTalks: Understanding Lecithin Cholesterol Acyltransferase (LCAT) Deficiency Disorders with Dr. Marina Cuchel https://www.youtube.com/watch?v=R_r-ZnQcOwM : 2024.

Santos RD, Cuchel M.: LDL-C-Lowering Therapies for Adults and Children With Homozygous Familial Hypercholesterolemia: Challenges and Successes Circulation 149 : 363-366,2024.

McGowan MP, Cuchel M.: Universal paediatric screening for familial hypercholesterolaemia Lancet 403 : 6-8,2023.

McGowan MP, Cuchel M, Lee PC.: USPSTF Recommendation on Screening for Lipid Disorders in Children and Adolescents JAMA 330 : 2023-2024,2023.

Lan NSR, Bajaj A, Watts GF, Cuchel M.: Recent advances in the management and implementation of care for familial hypercholesterolaemia Pharmacol Res 194 : 106857,2023.

Academic Contact Information

Institute for Translational Medicine and Therapeutics
9017 Maloney Building
3600 Spruce Street
Philadelphia, PA 19104
Phone: 215-662-7188