Aziz Rangwala
Education:
Sc.B. Brown University (2017)
Current Position:
7th Year MSTP
3rd Year Medical Student
Advisor:
Markus Seeliger
Graduate Program:
Molecular & Cellular Biology
Research Interest:
I am interested in how structure-kinetics relationships and allosteric regulation of proteins can be
applied to rational drug design against targets dysregulated in human disease. My previous
research involved studying molecular mechanisms of neurodegeneration in Alzheimer’s Disease
and Down Syndrome and elucidating how the antibiotic streptomycin causes misreading of the
bacterial genetic code.
Protein kinases, which are encoded in 2% of the human genome, are critical mediators of signal
transduction involved in many cellular processes. Kinase dysregulation is a major driver of
oncogenesis and autoimmune disorders, making the family an attractive target for therapeutic
intervention. My thesis work centers on how mutations in Abl kinase cause resistance to small
molecule inhibition by affecting drug-target residence time and interactions with chaperone
proteins. I am also involved in developing potent and selective inhibitors for cyclophilin family
proteins.
Publications:
1. Peterson, A.A.*; Rangwala, A.M.*; Thakur, M.K.; Ward, P.S.; Hung, C.; Outhwaite,
I.R.; Chan, A.I.; Usanov, D.L.; Mootha, V.K.; Seeliger, M.A.; Liu, D.R. Discovery and
Molecular Basis of Subtype-Selective Cyclophilin Inhibitors. Nat Chem Biol (Accepted
2022)
* Co-first author
2. Mingione, V.R.; Foda, Z.H.; Paung, Y.; Philipose, H.; Rangwala, A.M.; Shan, Y.;
Seeliger, M.A. Validation of an Allosteric Binding Site of Src Kinase Identified by
Unbiased Ligand Binding Simulations. Journal of molecular biology 2022, 167628,
doi:10.1016/j.jmb.2022.167628.
3. Rangwala, A.M.* † ; Mingione, V.R.*; Georghiou, G.; Seeliger, M.A. † Kinases on Double
Duty: A Review of UniProtKB Annotated Bifunctionality within the Kinome.
Biomolecules 2022, 12, 685.
* Co-first author, † Co-corresponding author
4. Rangwala, A.M. † ; Berger, B.T.; Robers, M.B.; Knapp, S.; Seeliger, M.A. † Resistance to
kinase inhibition through shortened target engagement. Mol Cell Oncol 2022, 9,
2029999, doi:10.1080/23723556.2022.2029999.
† Co-corresponding author
5. Lyczek, A.*; Berger, B.T.*; Rangwala, A.M.*; Paung, Y.; Tom, J.; Philipose, H.; Guo,
J.; Albanese, S.K.; Robers, M.B.; Knapp, S.; Chodera, J.D.; Seeliger, M.A. Mutation in
Abl kinase with altered drug-binding kinetics indicates a novel mechanism of imatinib
resistance. Proc Natl Acad Sci U S A 2021, 118, e2111451118,
doi:10.1073/pnas.2111451118.
* Co-first author
6. William, C.M.; Saqran, L.; Stern, M.A.; Chiang, C.L.; Herrick, S.P.; Rangwala, A.;
Albers, M.W.; Frosch, M.P.; Hyman, B.T. Activity-Dependent Dysfunction in Visual and
Olfactory Sensory Systems in Mouse Models of Down Syndrome. J Neurosci 2017, 37,
9880-9888, doi:10.1523/JNEUROSCI.1045-17.2017.
