Kyle Hoffmann is currently a graduate student studying under Professor de Pablo. He received his bachelor's in chemical engineering from the University of Delaware in 2009. He then began pursuing a PhD in chemical and biological engineering from the University of Wisconsin-Madison. He received funding from the Computation and Informatics in Biology and Medicine Training Program for his first three years as a graduate student. While still a graduate student at the University of Wisconsin-Madison, he is currently completing his PhD research at the University of Chicago.
Kyle is originally from Seaville, New Jersey. He graduated from Ocean City High School in 2005. He enjoys activities such as reading, hiking, and dancing.
The protein amylin has been implicated in the formation of Type II Diabetes. It aggregates to form long fibrils, causes membranes leakage, and can induce the death of the Beta cells involved in the production of insulin. While humans develop Type II Diabetes, some other mammals such as rats and mice do not develop the disease. However, if the human version of amylin is transgenically inserted into rats, they then develop Type II Diabetes-like symptoms. The ability of the human version of amylin to form aggregates is posited as one possible reason why humans develop Type II Diabetes while some species such as rats do not.
Kyle’s research seeks to understand how human amylin aggregates and disrupts lipid membranes. He uses molecular dynamics simulations coupled with advanced sampling techniques to study these systems. The first goal of this research is to calculate the free energy landscape of amylin as a monomer in an aqueous solution as a function of α-helical and β-hairpin content. This will determine which secondary structures are most predominant in solution and determine the best parameters for further study. Next, he is studying the effect of lipid bilayers on the structure and how it influences a transition from a predominantly random coil to an α-helical structure. At each step, the human and rat versions of amylin are compared to understand how a difference in only six residues leads to such different physiological properties.
These studies are performed using atomistic molecular dynamics simulations. Because the time scale on which protein folding and aggregation occur is much larger than simulations are able to access, advanced sampling techniques such as replica exchange, umbrella sampling, metadynamics, and bias exchange simulations are used to study the free energy properties and transitions of the system.
In the future, these techniques will be extended to study how dimers and other oligomers form. He will also study how lipid bilayers change these structures and catalyze aggregation. Finally, he will study how the oligomers disrupt lipid bilayers.
Colón, Yamil J., et al. "Free energy of metal-organic framework self-assembly." The Journal of chemical physics 150.10 (2019): 104502.
Membrane permeation versus amyloidogenicity: a multitechnique study of islet amyloid polypeptide interaction with model membranes
Martel, Anne, et al. "Membrane permeation versus amyloidogenicity: a multitechnique study of islet amyloid polypeptide interaction with model membranes." Journal of the American Chemical Society 139.1 (2016): 137-148.
Hoffmann, Kyle Quynn, et al. "Secondary structure of rat and human amylin across force fields." PloS one 10.7 (2015): e0134091.
Perry, Sarah L., et al. "Chirality-selected phase behaviour in ionic polypeptide complexes." Nature communications 6 (2015): 6052.
Hoffmann, K. Q., et al. "A molecular view of the role of chirality in charge-driven polypeptide complexation." Soft Matter 11.8 (2015): 1525-1538.
J. Qin, D. Priftis, R. Farina, S. L. Perry, L. Leon, J. Whitmer, K. Hoffmann, M. Tirrell, and J. J. de Pablo . Interfacial Tension of Polyelectrolyte Complex Coacervate Phases. ACS Macro Letters. 2014. Vol. 3, Pg. 565-568.