Amer Alam, PhD
Structural Biology of Membrane Transport
Born in Lahore, Pakistan, Amer moved to the United States in 1998, graduating from Lamar High School in Houston, TX, before getting his undergraduate degree in Biochemistry from the University of Houston. He then moved on to get his Ph.D. under the supervision of Dr. Youxing Jiang at UT Southwestern Medical Center in Dallas, TX, specializing in X-ray crystallographic and biochemical studies of the non-selective tetrameric cation channel NaK. The high-resolution structural studies led to several advancements in the understanding of ion selectivity and gating properties for this large family of transmembrane proteins. Amer then moved to Zürich, Switzerland, to start his postdoctoral work with Dr. Kaspar Locher at ETH Zürich, where he focused primarily on the structural analysis of human ABCB1 (p-glycoprotein/p-gp/MDR1), an ATP binding cassette (ABC) transporter first identified as a primary player in acquired multidrug resistance of certain tumors. Amer determined several cryo-EM structures of ABCB1 in various conformations in apo-form or in complex with substrates or inhibitors, yielding important insight into the mechanisms of inhibitor or substrate discrimination by this physiologically and medically relevant membrane transport protein. In addition to his work on ABCB1, Amer also determined the crystal structures of a complex of vitamin B12 (cobalamin) bound human Transcobalamin and its cognate cell surface receptor TCBlR/CD320 during his postdoctoral work.
Amer moved to Minnesota with his wife and young son to work at the Hormel Institute and continue his work on deciphering the molecular details of membrane transport processes, taking advantage of the Institute’s state of the art cryo-EM facility. The Hormel Institute ranks amongst a handful of elite institutions housing a Titan Krios microscope combined with a direct electron detector, a setup designed to obtain near-atomic resolution (routinely achieving better than 0.5 nanometer resolution). This allows for accurate visualization of the molecular details underlying the functioning of macromolecules and has revolutionized structural biology and allowed for targeting of complex biological problems previously considered off-limits to high resolution visualization Such insight is invaluable in obtaining molecular details of membrane protein interactions with drugs, transport substrates, and inhibitors and can aid in the design of novel therapeutics targeting diseases stemming from membrane protein dysfunction.
Personal interests and hobbies
Amer and his family are big fans of the outdoors and take every opportunity to run, bike, or trek both for recreation and commuting (when safe). Amer and his wife are fans of long distance running and hope to one day complete the 56-kilometer Two Oceans marathon in Cape town, South Africa together. The running serves a key purpose in allowing for the consumption of large quantities of food that they like to prepare in their kitchen, which Amer views as a second lab. Amer has a broad range of musical tastes and thinks he may be able to play the guitar (mostly Spanish/classical). Amer is also obsessed with lego, something he has passed onto his toddler son, and credits it with being the reason he got in to structural biology. He has also dabbled in construction work and is particularly proud of a series of concrete countertops he once poured.
High School: Lahore College of Arts and Sciences (LACAS), Lahore, Pakistan (grades 9-11), Lamar High school, Houston, TX (12th grade)Undergraduate: University of Houston (Major: Biochemistry, Minor: Chemistry)
Graduate School: University of Texas, Southwestern Medical Center, Dallas, Texas (Youxing Jiang Lab, Department of Physiology/ Howard Hughes Medical Institute)
Postdoctoral training: ETH Zürich, Zurich Switzerland (Kaspar Locher Lab, Institute of Molecular Biology and Biophysics, Department of Biology).
Masonic Cancer Center, University of Minnesota
The Alam lab uses a combination of biochemical and structural (Cryo-EM and X-ray crystallography) techniques to primarily study macromolecules and macromolecular complexes involved in membrane transport, homeostasis, and biogenesis, with a particular focus on pinpointing lipid/protein interactions in context of membrane protein function. Maintenance of membrane bilayer integrity and tight control over material transfer across cellular and organellar membranes is central to proper physiological functioning. Dysfunction of these systems lies at the heart of several devastating, often fatal pathologies ranging from rare inherited diseases such as Zellweger’s syndrome and adrenoleukodystrphy (both stemming from peroxisomal dysfunction) to a range of neurodegenerative disorders, diabetes, and cancer.
- EMBO Long term postdoctoral fellowship (ALTF 770-2010)
- Deans Discretionary Award recipient 2009 UTSW
- Funded by Molecular Biophysics Training grant T32 GM008297, 2007-2009
- Undergraduate Research Grant, Department of Biology and Biochemistry, University of Houston, 2001
- Structure of the human lipid exporter ABCB4 in a lipid environment.
Olsen JA, Alam A, Kowal J, Stieger B, Locher KP.
Nat Struct Mol Biol. 2020 Jan;27(1):62-70. doi: 10.1038/s41594-019-0354-3. Epub 2019 Dec 23.
- Alam A, Kowal J, Broude E, Roninson I, Locher KP. Structural insight into substrate and inhibitor discrimination by human P-glycoprotein. Science 2019 Feb 15;363(6428):753-756.
- Alam A, Küng R, Kowal J, McLeod RA, Tremp N, Broude EV, Roninson IB, Stahlberg H, Locher KP. Structure of a zosuquidar and UIC2-bound human-mouse chimeric ABCB1. Proc Natl Acad Sci U S A. 2018 Feb 27;115(9):E1973-E1982
- Alam A, Woo JS, Schmitz J, Prinz B, Root K, Chen F, Bloch JS, Zenobi R, Locher KP. Structural basis of transcobalamin recognition by human CD320 receptor. Nat Commun. 2016 Jul 14;7:12100.
- Alam A, Jiang Y. Structural studies of ion selectivity in tetrameric cation channels. J Gen Physiol. 2011 May;137(5):397-403
- Alam A, Jiang Y. High-resolution structure of the open NaK channel. Nat Struct Mol Biol. 2009 Jan;16(1):30-4.
- Alam A, Jiang Y. Structural analysis of ion selectivity in the NaK channel. Nat Struct Mol Biol. 2009 Jan;16(1):35-41.
- Alam A, Shi N, Jiang Y. Structural insight into Ca2+ specificity in tetrameric cation channels. Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15334-9.
Complete list of publications:
Primary Research Areas
- Membrane transport processes
- Peroxisome biogenesis and homeostasis
- Lipid/protein interactions
- Lipid and fatty acid metabolism
- Membrane protein biochemistry
- Cryo electron microscopy
- X-ray crystallography
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