Research Interests
Research Interests
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Copyright Alex Cagan (2022)
The BIG QUESTION in my research program is...
The BIG QUESTION in my research program is...
"How do proteins with similar structures carry out different functions?"
"How do proteins with similar structures carry out different functions?"
To answer this question, I use multiplexed assays of variant effects and protein evolution methods to create topographical maps of protein mutational space. By introducing all possible mutations to a protein, we can tell which sets of mutations change the protein's function. From there, we can determine if the protein's amino acid sequence results in it being a "generalist" or a "specialist".
To answer this question, I use multiplexed assays of variant effects and protein evolution methods to create topographical maps of protein mutational space. By introducing all possible mutations to a protein, we can tell which sets of mutations change the protein's function. From there, we can determine if the protein's amino acid sequence results in it being a "generalist" or a "specialist".
I am particularly interested in applying these technologies to understand protein diversity and function in the blood coagulation system. These studies have the potential to lead to novel therapeutics, as well as unravel the mysteries of protein specificity and function.
I am particularly interested in applying these technologies to understand protein diversity and function in the blood coagulation system. These studies have the potential to lead to novel therapeutics, as well as unravel the mysteries of protein specificity and function.
To reach these research goals, I use a combination of approches from biochemistry, genetics and evolutionary biology.
To reach these research goals, I use a combination of approches from biochemistry, genetics and evolutionary biology.
Selected Publications
Selected Publications
Baid S, Holding ML, Laurin T*, Siemieniak D, Ginsburg D, and Haynes LM. (2026) Mapping the mutational landscape for streptokinase binding to plasminogen. J. of Thromb. Haemost, Epub ahead of print. *Undergraduate researcher
Holding ML, Pontius MHH, Ward MS*, Akhtar J, Crowell HL, Svilar D, Keeler KM, Haynes LM, Ginsburg D, and Shavit J. (2026) Deconstructing cardiovascular and coagulation-related traits reveals multi-functional snake venom specificity. Evolution, PMID: 41811938 *Undergraduate researcher
Ward MS*, Holding ML, Haynes LM, Margres MJ, Matocq MD, and Ginsburg D. (2025) Tandem duplication of serpin genes yields functional variation and snake venom inhibitors. Mol. Biol. Evol., PMID: 41218074 *Undergraduate researcher
Haynes LM, Holding ML, Woodard J, Siemieniak D, and Ginsburg D. (2025) Thermodynamics and selection of the plasminogen activator inhibitor-1 latency transition. J. Biol. Chem., PMID: 41197721
Holding ML*, Disharoon D*, Haynes LM*, Chakravarthy Paruchuri B, Pontius MHH, Golden K, Shavit HA, Desch KC, Ginsburg D, Sen Gupta A, Cruz Y, Drabeck DH. (2025) Comparative microfluidic and enzymatic analyses reveal multifaceted snake venom resistance and novel VWF behavior in the opossum Monodelphis domestica. PLoS One, PMID: 40971373 *Co-authors contributed equally
Haynes LM, Holding ML, DiGiovanni HL*, Siemieniak D, and Ginsburg D. (2025) High-throughput amino acid-level characterization of the interactions of plasminogen activator inhibitor-1 with variably divergent proteases. Protein Sci., PMID: 39345533 *Undergraduate researcher
Haynes LM, Huttinger ZM, Yee A, Kretz AC, Holding ML, Siemieniak DR, Lawrence DA, Ginsburg D. (2022) Deep mutational scanning and massively parallel kinetics of plasminogen activator inhibitor-1 functional stability to probe its latency transition. J. Biol. Chem., PMID: 36257408
Huttinger ZM*, Haynes LM*, Yee A, Kretz AC, Holding ML, Siemieniak DR. Lawrence DA, Ginsburg D. (2021) Deep mutational scanning of the plasminogen activator inhibitor-1 functional landscape. Sci. Rep., 11, 18827. PMCID: 34552126 *Co-authors contributed equally
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