Page 12 - Hormel Institute Annual Report 2021-22

Current research projects:
1. Structural Basis of fatty acid trans- port by peroxisomal ABC transporters
2. ABCA7 in Alzheimer’s Disease Patho- genesis
3. ABCB1 in targeted Cancer Therapy
Amer Alam, PhD
“We aim to understand the underlying chemistry governing the function of molecular machines involved in the transport of biomaterials across cell membranes,
a process essential to cellular physiology.”
Amer Alam
12 | THE HORMEL INSTITUTE // Structural Biology of
Membrane Transport
ASSISTANT PROFESSOR
UNIVERSITY OF MINNESOTA
We use a combination of biochemistry and structural biology tools to study human membrane transport proteins
involved in shuttling biomaterials across organ- ellar and cellular membranes. A major focus
of our lab is on the study of ABC transporters, one of the largest protein superfamily across all kingdoms of life, that underlie many physiologi- cally essential processes such as lipid and fatty acid transport and xenobiotic clearance. Using our in-house Titan Krios cryo-electron micro- scope, our lab has recently determined high resolution structures of several different human ABC transporters, resolution, providing funda- mental insight into their molecular organization and conformational landscape. These include ABCA7, a phospholipid and sterol transporter who’s dysfunction contributes to Alzheimer’s Disease pathogenesis, for which we were award- ed a 2-year R21 grant (PI:Alam) from the NIH Institute on Aging. We also determined struc- tures of human ABCD1, a peroxisomal protein that controls the passage of specific fatty acids into the peroxisome for their metabolism and whose dysfunction can lead to severe metabolic and neurological pathologies including X-linked
Adrenoleukodystrophy. Our ABCD1 project is supported by a 4 year R01 grant from the NIH National Institute of General Medical Sciences (PI:Alam). Additionally, we have determined structures of human ABCB1, a multidrug exporter included on the FDA’s list of essential transporters to screen all devel-opmental drugs against due to its wide substrate specificity, ubiquitous expression, and strong influence on drug pharmacokinetics and drug-drug interac- tions Our ABCB1, also known as MDR1, can play a key role in development of multidrug resis- tance in cancer cells and chemotherapy failure. Our structures of MDR1 bound to different inhibitors helps revel the chemistry behind the transport of drugs by MDR1 and its inhibition.