Session: 20-17-01: Rising Stars of Mechanical Engineering

Paper Number: 172582

Controlling Coagulation 

Hemostasis — the process of generating blood clots — is a rapid, multi-step, and highly regulated cascade to minimize blood loss. This physiological process is impaired in many diseases, resulting in pathological bleeding or clotting. Because the hemostatic system is complex and can become deranged in many ways, the only practical approach to capturing and treating coagulation disorders is to employ computational modeling. My group pioneered the use of feedback control theory to manipulate the concentrations of proteins that are involved in inflammation-mediated coagulation disorders. Two such disorders are: (1) trauma-induced coagulopathy, which includes hemorrhage after severe trauma and shock with poor treatment outcomes; and (2) infection-induced coagulopathy in the lung, which results in deposits of fibrin, the final protein of the coagulation process, in inflamed lungs that can cause irreversible scar formation called pulmonary fibrosis. For both disorders, four needs exist: mechanism capture, dimension reduction, rapid decision support, and treatment personalization. We explained how: simple input-output mathematical models capture biological knowledge independent of patient characteristics, for both trauma-induced coagulopathy (Menezes et al., 2017) and for the complex dynamical interplay between inflammation, coagulation, and fibrinolysis that induces fibrin accumulation in inflamed lungs (Shick et al., 2025); model simplicity facilitates quick model run times and a potential replacement of time-consuming laboratory-based coagulation tests (Ghetmiri, Venturi, Cohen, Menezes, 2024); coagulation differences may be attributed to blood protein concentration discrepancies (Ghetmiri, Cohen, Menezes, 2021); and appropriately changing protein concentrations results in suitable coagulation control (Ghetmiri and Menezes, June 2023). We confirmed such manipulation in vitro, which sets the stage for future targeted, personalized in vivo interventions. This calls for automation that accomplishes the tailored and real-time delivery of blood products and/or protein therapeutics. However, biomolecular systems belong to the class of dynamical systems whose states are restricted to non-negative values. My group advanced the theory of such systems to program biosystem robustness. For the human coagulation positive system, we developed a satisfactorily-performing controller that copes with an uncertain state-dependent input delay and compensates for a control input that can saturate (Ghetmiri and Menezes, May 2023). This controller assumed linear system dynamics, and we then showed that the human coagulation positive system belongs to the class of positive systems for which an additional controller is required to regulate nonlinear dynamics (Liu and Menezes, 2024). For the pulmonary fibrin accumulation positive system, we established that dynamic therapy using protein feedback control is feasible (Shick, Liu, Menezes, 2025).

Presenting Author: Amor Menezes University of Florida

Presenting Author Biography: Amor A. Menezes is an Associate Professor of Mechanical and Aerospace Engineering at the University of Florida, with affiliate appointments in Biomedical Engineering, Agricultural and Biological Engineering, Genetics, and Chemical Engineering. He is a member of the National Academies of Sciences, Engineering, and Medicine Standing Committee on Advances and National Security Implications of Transdisciplinary Biotechnology. His research focuses on modeling and controlling biological processes for medical and space applications. His group develops feedback control systems for inflammation-mediated coagulation disorders; advances the theory of biomolecular positive dynamical systems; designs integrated space biomanufacturing systems; and genetically engineers microbes to reject extreme environments. As Principal Investigator of three multi-university experiments launched to the International Space Station, he established the viability of space microbial biomanufacturing. From 2017-2023, he was Science Principal Investigator of NASA's Center for the Utilization of Biological Engineering in Space. Prof. Menezes' research was recognized by the NSF CAREER award, the Synthetic Biology Leadership Excellence Accelerator Program, and the Emerging Leaders in Biosecurity Initiative. He has contributed to the Engineering Biology Research Consortium's "Engineering Biology for Space Health Roadmap", the White House Office of Science and Technology Policy workshop on "Homesteading in Space", and the National Intelligence Council Strategic Futures Group's "Global Trends Report". He is an Associate Editor of the IEEE Control Systems Society Technology Conference Editorial Board and the ASME Modeling, Estimation and Control Conference Editorial Board. He is a Senior Member of IEEE and a Member of AIAA, ASME, and ASGSR. Prof. Menezes received a Ph.D. in aerospace engineering from the University of Michigan, and completed postdoctoral training in aerospace engineering and bioengineering at the University of Michigan and the University of California, Berkeley, respectively.

Authors:

Amor Menezes University of Florida