Research Interests

The BIG QUESTION in my research program is...

"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".

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. 

Representative Papers

1. 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. bioRxiv 500671 [Preprint]. July 20, 2022 [cited 25 July 2022] Available from: https://doi.org/10.1101/2022.07.19.500671 

2. 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 

Previous Research

As a classically trained protein biochemist specializing in blood coagulation,  my graduate training focused on understanding how blood flow dynamics affect the kinetics of the coagulation process. 

1. Nelson A, Kelley MA, Haynes LM, Leiderman K. (2021) Mathematical models of fibrin polymerization: Past, present, and future. Curr. Opin. Biomed. Engin., 20, 100350. 

2. Haynes LM, Orfeo T, Mann KG, Everse SJ, and Brummel-Ziedins, KE. (2017). Probing the dynamics of clot-bound thrombin at venous shear rates, Biophys. J., 112 (8), 1634-1644. PMCID: 28445754 

3. Haynes LM, Bouchard BA, Tracy PB, and Mann KG. (2012) Prothrombin activation by platelet-associated prothrombinase proceeds through the prethrombin-2 pathway via a concerted mechanism. J. Biol. Chem., 287 (46), 38647-38655. PMCID: PMC3493909 

4. Haynes LM, Orfeo T, and Mann KG (2012) Rivaroxaban delivery and reversal at a venous flow rate, Arterioscler. Thromb. Vasc. Biol., 32 (12), 2877-2883. PMCID: PMC3629550 

5. Haynes LM, Dubief YC, and Mann, KG. (2012) Membrane binding events in the initiation and propagation phases of tissue factor initiated zymogen activation under flow, J. Biol. Chem., 287 (8), 5225-5234. PMCID: PMC3031058 

6. Haynes LM, Dubief YC, Orfeo T, and Mann KG. (2011) Dilutional control of prothrombin activation at physiologically relevant shear rates. Biophys. J., 100 (3), 765-773. PMCID: PMC3031058 

A complete list of my published works can be found here.