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.
Mutational Scanning Symposium 2024
Mutational Scanning Symposium 2024
I presented our latest work work mapping allosteric signaling networks in PAI-1.
Mutational Scanning Symposium 2022
Mutational Scanning Symposium 2022
I presented a lightning talk on our latest work evolving serine protease inhibitors to have novel specificity at the Mutational Scanning Symposium in Toronto, ON, in June 2022.
Recent Publications
Recent Publications
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
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