Faculty Profile

Francis J. Doyle III, PhD


Professor of Bioengineering, Harvard Paulson School of Engineering & Applied Sciences

Administrative Title(s)

Dean, Harvard John A. Paulson School of Engineering and Applied Sciences

See publications


Address

Harvard John A. Paulson School of Engineering and Applied Sciences
29 Oxford Street
Cambridge, MA 02138
USA

Phone 617-495-5829

Email frank_doyle@seas.harvard.edu
Email darone@seas.harvard.edu

Society Memberships

Society for Research on Biological Rhythms,
American Institute for Medical & Biological Engineering,
American Diabetes Association

Research Interests

With a background in traditional process control, my research program is focused on biosystems analysis and control, with an eye to both unraveling the complex regulatory circuitry that underlies biological networks, as well as reverse-engineering principles of biological control for subsequent application in engineering systems. We bring tools from systems engineering, including nonlinear dynamics, system identification, and control design, to unravel the complex feedback architectures in nature. Our work in systems biology has made important contributions towards understanding an array of diseases and biological systems, including: the unfolded protein response, type 2 diabetes, heat stroke, PTSD, and Alzheimer’s. The largest and most impactful body of our work in this field has centered on the rich regulatory architecture underlying circadian rhythm generation in the brains of flies and mammals. Focusing on network aspects of the clock, both at the gene regulatory level and the intercellular coupling scale, our group was the first to publish experimentally validated mathematical predications, that phenotypes at the cellular level contradict the behavior observed at the organism or tissue level. This has profound implications for the study of clock neurons in the brain. In a collaboration with biologists at USC, our group detailed the use of mathematical models and systems analysis to identify, for the first time, novel small molecules that target directly the circadian clock. The crucial role of our group was identifying a novel spatiotemporal control mechanism that elucidates the role of these molecules in modifying protein stability.

Trainees

FORMER GRADUATE STUDENTS (7 MS, 35 PhD)
Joon Bok Lee (Ph.D. Chemical Engineering, 6/16),
Personalization and Enhanced Designs for Automated Glucose Control in Artificial Pancreas (employed at Insulet)
Lauren Huyett (Ph.D. Chemical Engineering, 6/16),
Impact of Sensing and Actuation Characteristics on Artificial Pancreas Design (employed at Agilent)
Peter St. John (Ph.D., Chemical Engineering, 6/15),
Novel Targets in the Circadian Clock (employed at NREL)
Felipe Nuñez (Ph.D., Elec. Eng., 9/14),
Bio-inspired Algorithms for Mobile Ad Hoc Wireless Networks (faculty member at Pontificia Universidad Catolica de Chile)
Justin Lee (Ph.D., Chemical Engineering, 9/14),
Artificial Pancreas Design Using Inhalable Insulin (employed at   Exxon-Mobil)
Rebecca Harvey (Ph.D., Chemical Engineering, 9/13),
Development and Implementation of the Health Monitoring System for the Artificial Pancreas (employed at Air Products)
Jamilah Abdur-Rahim (Ph.D., Mech. Eng., 9/12),
Identification of Control for Learning in Visual-Motor Skill (post-doc at Advanced Telecommunications Research Institute, Japan)
Theresa Yuraszeck (Ph.D., Chemical Engineering, 3/11),
Modeling the Unfolded Protein Response in Yeast (employed at Amgen)
Henry Mirsky (Ph.D., BMSE, 4/10),
Modeling and Analysis of the Mammalian Circadian Clock (employed at DuPont)
Matthew Percival (Ph.D., Chemical Engineering, 6/10),
Modeling and Control of Glycemia in Type 1 Diabetes Mellitus (employed at Theranos)
Jason Shoemaker (Ph.D., Chemical Engineering, 3/09),
Design Principles in Biological Networks: Balancing Efficacy with Robustness (faculty member at University of Pittsburgh)
Stephanie Taylor (Ph.D., Computer Science, 6/08),
Computational Methods for the Analysis of Phase Dynamics in Biological Oscillators (faculty member at Colby College)
Neda Bagheri (Ph.D., Elec. Eng., 11/07),
Phase as a performance metric for the analysis, control, and model development of circadian gene networks (faculty member at Northwestern)
Mustafa Dokucu (Ph.D., Chemical Engineering, 10/07),
Reduced Order Methodologies for the Control of Particle Size Distribution in Emulsion Polymerization (employed at GE)
Mehmet Mercangoz (Ph.D., Chemical Engineering, 6/07),
Distributed Model Predictive Control of Large – Scale Process Systems (employed at ABB)
Rachel Gillis (M.S., Chemical Engineering, 6/07),
Glucose Estimation and Prediction with Model Predictive Control for Type 1 Diabetes (employed at Tennessee Eastman)
Kapil Gadkar (Ph.D., Chemical Engineering, 3/05),
Large Scale Model Identification in Systems Biology (employed at Theranos)
Camelia Owens (Ph.D., Chemical Engineering, 6/04),
Robust Regulation of Glucose in Diabetic Patients (employed at the National Institutes of Health)
Nicholas Hernjak (Ph.D., Chemical Engineering, 3/04),
Characterization of Process Nonlinearity (employed at ExxonMobil)
Jörg Stelling (Ph.D. 1/04, Mechanical Engineering, University of Stuttgart),
Systems Analysis of Robustness in Cellular Networks (faculty member at ETH)
Toby Junker (Ph.D., Chemical Engineering, 9/03),
Modeling and Control of a Continuous Thermo-Evaporation Process for Production of Thin Film Photovoltaic Modules (employed at Fuel Cell Energy)
Dan Saffer (Ph.D., Chemical Engineering, 5/03),
Advanced Cross-Direction Control of Sheet and Film Processes (employed at Alcoa)
Darrin Feather (M.S., Chemical Engineering, 12/02),
Grade Transition Control in Polymerization Reactors (employed at Weyerhaeuser)
Charles Immanuel (Ph.D., Chemical Engineering, 11/02),
Experimental Control Studies of a Semi-batch Emulsion Polymerization Reactor (faculty member at Imperial College)
Radhakrishnan Mahadevan (Ph.D., Chemical Engineering, 6/02),
Dynamic Nonlinear Input-Output Control (faculty member at U. Toronto)
Jorge Castro-Velez (Ph.D., Chemical Engineering, 9/01),
Mill-wide Control Using Specialized Algorithms for Parallel Large Scale MPC (employed
DuPont Company)
Rajanikanth Vadigepalli (Ph.D., Chemical Engineering, 6/01),
Second Messenger Modeling of Neuromodulatory Pathways (faculty member at Thomas Jefferson Medical University)
Alan Mahoney (Ph.D., Chemical Engineering, 4/01),
Modeling of Population Balance Equation Descriptions of Precipitation (faculty member at Sheffield University)
Ed Gatzke (Ph.D., Chemical Engineering, 6/00),
An Intelligent Approach to Process Monitoring and Control (faculty member at Univ. South Carolina)
Luis Puig (M.S., Chemical Engineering, 4/00),
Grade Transition Control in a Pulp Digester (faculty member at U. Mexico)
Robert Parker (Ph.D., Chemical Engineering, 6/99),
Biosystems Model-based Control (faculty member at University of Pittsburgh)
Arkan Kayihan (M.S., Chemical Engineering, 7/98),
Local Nonlinear Control of a Process Actuator (employed at  Aspen Technology)
Kairali Podual (Ph.D., Chemical Engineering, 7/98),
Complex Hydrogel Design for Control-Relevant Insulin Delivery (employed at BioArray Solutions)
Tom Kendi (Ph.D., Chemical Engineering, 8/97),
Constrained Control of Nonlinear Process Systems (employed at ExxonMobil)
Philip Wisnewski (Ph.D., Chemical Engineering, 8/97),
Model Reduction, State Estimation and Model Predictive Control of a Kamyr Digester (employed at Weyerhaeuser)
Lalitha Balasubramhanya (Ph.D., Chemical Engineering, 7/97),
Low Order Models for Nonlinear Process Control (employed at Applied Materials)
Harpreet Kwatra (Ph.D., Chemical Engineering, 6/97),
A Neuro-mimetic Dynamic Gain Scheduled Process Control (employed at Envision Financial Systems)
Christie Dorski (M.S., Chemical Engineering, 12/96),
Dynamic Behavior of Glucose-Responsive Poly (Methacrylic Acid-g Ethylene Glycol) Hydrogels
Andre Shaw (Ph.D., Chemical Engineering, 8/96),
A Dynamic Neural Network for Nonlinear Process Modeling and Control (employed at ExxonMobil)
Bryon Maner (Ph.D., Chemical Engineering, 7/96),
Polymerization Reactor Control Using Computationally Tractable Input-Output Models (employed at Air Products)
Douglas Heemstra (M.S., Chemical Engineering, 3/96),
Practical Nonlinear Model Identification and Control Implementation (employed at Hoechst Celanese)
Alex Stack (M.S., Chemical Engineering, 9/95),
The Optimal Control Structure: A Measure for Control-Relevant Nonlinearity (employed at Blake, Cassels, & Graydon)
 
PRESENT AND FORMER POSTDOCTORAL FELLOWS

Dr. Zixi Cheng (1/96 - 9/97) (faculty member at U. Kentucky)
Dr. Scott Meadows (1/98 - 6/00) (faculty member at U. Alberta)
Dr. Tim Crowley (3/98 - 10/00) (employed at United Technologies)
Dr. Tahsin Bahar (11/99 - 5/00) (employed at Marmara Research Center, Turkey)
Dr. Pascal DuFour (7/00 - 7/01) (faculty member at Lyon University, France)
Dr. Sharad Bhartiya (7/00 – 8/02) (faculty member at IIT, Bombay)
Dr. Selwa Ben Amor (11/00 – 12/02)
Dr. Yang Wang (9/01 – 8/03) (employed at Yield Dynamics)
Dr. Myung-June Park (3/03 – 3/06) (employed at Mt. Sinai School of Medicine)
Dr. Rudiyanto Gunawan (8/03 – 7/06) (faculty member at ETH)
Dr. Cesar Palerm (9/04 – 8/07) (employed at Medtronic)
Dr. Pau Herrero Vinas (3/07 – 11/07) (researcher at Hospital de la Santa Creu I Sant Pau, Barcelona)
Dr. Constantijn Sanders (10/05 – 12/08) (employed at Sanders Consulting, The Netherlands)
Dr. Peter Chang (10/06 – 12/08) (employed at DuPont)
Dr. Bharath Ananthasubramaniam (9/07 – 1/12) (Humboldt Fellow at Technical University of Munich)
Dr. Kalyan Gayen (9/07 – 7/09) (faculty member at IIT, Gandhinagar)
Dr. Osman Shahi (2/08 – 12/09) (employed at L’Oreal)
Dr. Youqing Wang (2/08 – 2/10) (faculty member at Beijing University of Chemical Technology)
Dr. Wenxue Wang (9/08 – 9/10)
Dr. Benyamin Grosman (9/08 – 12/11) (employed at Medtronic)
Dr. Yan Wan (2/09 – 7/09) (faculty member at University of North Texas)
Dr. Maria Rodriguez Fernandez (2/09 – 6/09, 5/10 – 4/14) (faculty member at Pontificia Universidad Catolica de Chile)
Dr. Camilla Luni (3/09 – 2/11) (post-doc at Padova University, Italy)
Dr. Yongqiang Wang (8/09 – 8/14) (faculty member at Clemson University)
Dr. Ruoting Yang (8/09 – 8/12) (post-doc at NIH)
Dr. Sriram Krishnamachari (9/09 – 12/11) (faculty member at IIIT, Delhi)
Dr. Chunhui Zhao (6/10 – 12/11) (faculty member at Zhejiang University)
Dr. Pegy Foteinou (8/10 – 11/12) (post-doc at Johns Hopkins University)
Dr. Klaske van Heusden (8/10 – 3/11) (post-doc at University of British Columbia)
Dr. Eyal Dassau (10/06 - present); presently a Senior Research Fellow at Harvard
Dr. Ravi Gondhalekar (7/12 – present)
Dr. Gunjan Thakur (9/12 – present)
Dr. Isuru Dasanayake (4/13 – present)
Dr. Alejandro Laguna (6/14 – present)
Dr. Sunil Agrawal (2/15 – present)
Dr. Pramod Rajaram (8/15 – present)
Dr. Stamatina Zavitsanou (10/15 – present)
Dr. Burook Misganaw (2/16 – present)
Dr. Ankush Chakrabarty (3/16 – present)
Dr. Edward Cao (2/16 – present)

Mentor(s)

Prof. Manfred Morari

Selected Publications

R.S. Parker, F.J. Doyle III, and N.A. Peppas, “A Model-based Algorithm for Blood Glucose Control in Type I Diabetic Patients”, IEEE Trans. Biomed. Eng., 46, 148-157, 1999.

H. P. Mirsky, A.C. Liu, D.K. Welsh, S.A. Kay, and F.J. Doyle III, “A Model of the Cell Autonomous Mammalian Circadian Clock”, PNAS, 106, 11107-11112, 2009.

T. Hirota, J. Lee, P. St. John, M. Sawa, K. Iwaisako, T. Noguchi, P. Pongsawakul, T. Sonntag, D. Welsh, D. Brenner, F.J. Doyle III, P. Schultz, and S. Kay, “Identification of Small Molecule Activators of Cryptochrome”, Science, 337, 1094-1097, 2012.

B.P. Kovatchev, E. Renard, C. Cobelli, H.C. Zisser, P. Keith-Hynes, S.M. Anderson, S.A. Brown, D.R. Chernavvsky, M.D. Breton, A. Farret, M.-J. Pelletier, J. Place, D. Bruttomesso, S. Del Favero, R. Visentin,  A. Filippi, R. Scotton, A. Avogaro, F.J. Doyle III, “Feasibility of Outpatient Fully Integrated Closed-loop Control: First Studies of Wearable Artificial Pancreas”, Diabetes Care, 36, 1851-1858, 2013.

E. Dassau, H. Zisser, R. Harvey, M. Percival, B. Grosman, W. Bevier, D.E. Seborg, L. Jovanovic, and F.J. Doyle III, “Clinical Evaluation of a Personalized Artificial Pancreas”, Diabetes Care, 36, 801-809, 2013.

P.C. St. John, T. Hirota, S.A. Kay, and F.J. Doyle III, “Spatiotemporal separation of PER and CRY post-translational regulation in the mammailian circadian clock”, Proc. Natl. Acad. Sci. USA, 111, 2040-2045, 2014.

F.J. Doyle III, L.M. Huyett, J.B. Lee, H.C. Zisser, and E. Dassau, “Closed-Loop Artificial Pancreas Systems: Engineering the Algorithms”, Diabetes Care, 37, 1191-1197, 2014.

G.S. Thakur, B.J. Daigle, Jr., K.R. Dean, Y. Zhang, M. Rodriguez-Fernandez, R. Hammamieh, R. Yang, M. Jett, J. Palma, L.R. Petzold, and F.J. Doyle III, “Systems Biology Aproach to Understanding Post-traumatic Stress Disorder”, Molecular BioSystems, 11, 980-993, 2015

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