Supramolecular dynamics of biological gels
Cell and molecular biology of airway clearance
Polymer physics of secretion
Polyelectrolyte dynamics of mucus gel
Laser scattering spectroscopy
Marine biopolymer dynamics
Polymer network theory and marine gel self-assembly
Gel formation and carbon cycling in the ocean
Cargo and release mechanism in secretion. The discovery that the dynamics of mucus swelling follows a Donnan equilibrium (NATURE,1981) paved the way to our discovery that mucus, as well as all secreted biopolymer matrices, is stored inside intracellular vesicles in the form of a condensed-phase polymer network and undergoes typical polymer gel phase transition upon release from the cell (Ciba Symp.1988, Biophys J.1991). These studies led to the formulation of a supramolecular model of mucus gel which is now the standard paradigm for understanding and further exploring the pathophysiology of airway diseases, stomach ulcers, and reproductive biology (Ann Rev Physiol. 1990, Cold Spring Harbor Perspect Med. 2012 ).
Intracellular signaling. Work on the understanding of the mechanisms whereby different intracellular organelles communicate to execute specific functions proved to be a significant advance and has been widely cited (NATURE 1998). The demonstration that intracellular signaling is encoded in discrete periodic quantal release of intracellular Ca2+ resulting from ion exchange via the interaction of K+ and Ca2+ intracellular ion channels was first conducted in our laboratory (Biophys J 2001, 2003). These observations established a new paradigm in the study of intracellular Ca oscillations and explained significant features of the pathophysiology of hypersecretory processes, as found in acute pancreatitis.
Marine biopolymer dynamics, gel formation, and carbon cycling in the ocean. Although critical to the survival of humans and other species, carbon cycling remains among the most pressing, yet least understood, issues in the global thermodynamics of our planet. The ocean is the second most important sink of atmospheric CO2. The output of this marine phytoplankton-based photosynthetic reactor consists of biopolymers that are released into seawater (FEBS Letters 2006). These biopolymers join a stock of organic molecules that contains about 700 billion tons of carbon, comprising one of earth’s largest global reserves of reduced organic carbon. Guided by engineering theory, we discovered that this huge mass of polymeric material can self-assemble forming microscopic gels that contain an estimated 70 (are the 700 and 70 figures correct?) billion tons of carbon (NATURE 1998) This seminal finding prompted us to formulate the hypothesis that self-assembled microgel must play a significant role in carbon cycling. Microgels are the primary source of nutrition for bacteria and thereby to higher trophic levels strongly impacting global elemental cycles (Faraday Disc Royal Soc Chem 2008). These observations were the basis of a $4.5M grant from the NSF Bioengineering Division and launched a new research program at the UW Friday Harbor Labs in 2001. Work on these ideas conducted during the following years received broad attention and led to the formulation of a fully testable hypothesis based on first principles set up a new paradigm in marine carbon cycling. Recently reviewed in the journal Gels, our work has gained broad recognition among colleagues in polymer physics, oceanography, geochemistry, and environmental engineering (Gels 2021).
BS Chemistry, University of Chile
MD University of Chile
Internship, Salvador General Hospital, School of Medicine, University of Chile, Santiago
Residence, Pediatric Cardiology, McKenna Children Hospital, SNS, Santiago, Chile;
NIH Senior Postdoctoral Fellow, Div. of Bioengineering and Div. Pediatric Cardiology
University of Washington, Seattle, WA.
I joined the Bioengineering faculty in 1974. Led by Professor Robert Rushmer, Bioengineering was still in a developmental stage and was structured as a Center jointly administered by the College of Engineering and the School of Medicine. As a Center, we had limited spport for education and began with a graduate program, I chaired the curriculum committee. In 1982, following my promotion to tenured Associate Professor, Director Lee Huntsman appointed me as Assistant Director of Bioengineering in charge of developing our first pilot Bioengineering Undergraduate Program. We designed a demanding curricular sequence, very similar to the MIT Undergraduate Bioengineering Program. It’s goal was to graduate a small cadre of exceptional individuals who could become leaders in shaping the emergence of Bioengineering, a field that was regarded at the time as a minor player by other Engineering and Medical School departments. As coordinator of this effort, I developed—and started teaching—a new class (Introduction to Bioengineering BE 299) with the aim of informing and recruiting future undergraduates. The class was well received by students and succeeded in attracting very strong students eager to undertake a demanding multi-discipine training.
Operated under the umbrella of the Inter-engineering Program of the College and funded in part by a generous grant from Hughes Foundation, the program was able to offer scholarships and support summer undergraduate research rotations. Working in laboratories of selected faculty from our Medical School and Engineering College most of our undergraduates ended their senior years well trained and with publications in refereed journals.
In 2000 this small, highly customized program was succeeded by a more usual BS Bioengineering degree program able to meet the University’s ambitions for larger numbers.
Nevertheless, by the time it was terminated our program shared the top position with the MIT Undergraduate Bioengineering in the ranking from the National Research Council. Over the period of it’s existence we graduated thirty-two students, all of whom were admitted to elite graduate MD, PhD, or MD/PhD programs, including Harvard, MIT, Yale, Hopkins, University of Washington, Michigan, Princeton, Berkeley, and UCLA among others. Almost all our former undergraduates from this program now occupy faculty positions in Medical or Engineering Colleges. Although it was limited in duration, I regard this experience as my most significant and rewarding academic contribution to Bioengineering, Medicine, and Engineering education at the University of Washington.
Over the following seventeen years after I moved my research to the UW Friday Harbor Laboratories, more than eighty undergraduates from different departments of our university and other universities applied and joined our laboratory. Funded by my NSF grant, which paid a modest salary, room, and board at FHL, they went through a demanding summer boot-camp learning polymer physics theory, methods including dynamic laser scattering, confocal microscopy, flow cytometry, etc., and rigorous laboratory training; they often ended with excellent publications. My residence at FHL set a shift to explore new horizons, it marked the most productive years of my academic career and were a welcome uplifting experience after my forced departure from my laboratory in Bioengineering.
USPHS. NIH Fogarty International Senior Postdoctoral Fellowship Award, NIH,1969-73
Appointment to NIH Cell Physiology Study Section 1983-87
Ordinary Fellow, Gonville & Caius College, University of Cambridge, UK, 1988
Outstanding Contribution to Undergraduate Education Award. University of Washington, 2004
Induction to the Faraday Div., Royal Society of Chemistry, York, UK 2007
Verdugo, P. (1980). Ca2+-dependent hormonal stimulation of ciliary activity. NATURE 283:764-765.
Tam, P.Y. and P. Verdugo (1981). Control of mucus hydration as a Donnan equilibrium process. NATURE 292:340-342.
Verdugo, P., P.Y. Tam and J. Butler (1983). Conformational structure of respiratory mucus studied by laser correlation spectroscopy. Biorheology 20:223-230.
Verdugo, P. (1984). Hydration kinetics of exocytosed mucins in cultured secretory cells of the rabbit trachea: A new model. Ciba Foundation Symposium: Mucus and Mucosa. Ciba Foundation London, 109:212-234.
Verdugo, P. and C. Golborne.(1988) Remote detection of ciliary movement by fiber optic laser-Doppler spectroscopy. IEEE Trans. Biomed. Eng. 35:303-308.
Fernandez, J. M., M. Villalón, and P. Verdugo (1991). Reversible condensation of mast cell secretory products in vitro. J. 59: 1022-1027.
Verdugo, P. (1990) Goblet cells and mucus secretion. Rev. Physiology. 52: 157-176.
Viney, C., Huber, A. E., and Verdugo, P. (1993). Liquid crystalline order in mucus. Macromolecules 26:852-257.
Verdugo, P., I. Deyrup-Olsen, A. W. Martin, and D.L. Luchtel (1992). Polymer gel phase transition: The molecular mechanism of product release in mucin secretion. In: Swelling of Polymer Networks. NATO ASI Series H, vol 64 pp 671-681, Ed: E. Karalis, Springer-Verlag, Heidelberg.
Verdugo, P. (1993) Polymer gel phase transition in condensation-decondensation of secretory products Poly. Sci. 110:146-155.
Chin, W-C., M.V. Orellana, and P. Verdugo. (1998) Formation of microgels by spontaneous assembly of dissolved marine polymers. NATURE 391: 568-572
Nguyen, T., W-C. Chin, and P. Verdugo. (1998) Role of Ca2+/K+ ion exchange in intracellular storage and release of Ca2+. NATURE 395:908-912
Quesada, I., W-C Chin, J. Jordan, P. Campos-Bedolla, & P. Verdugo (2001). Mouse mast cell secretory granules can function as intracellular ionic oscillators. J. 80:2133-2139.
Quesada, I., W-C Chin, & P. Verdugo (2003). ATP-Independent luminal Oscillations and release of Ca2+ and H+ from mast cell secretory granules: Implications for signal transduction. J. 85: 963-970.
Verdugo, P., A.L. Alldredge, F. Azam, D.L. Kirchman, U. Passow, & p. Santchi (2004). The oceanic gel phase: A bridge in the DOM-POM continuum. Marine Chemistry 92:65-66.
Quesada, I., Chin, W-C., & P. Verdugo. (2006) Mechanisms of signal transduction in photo-stimulated secretion in Phaeocystis globosa. FEBS Letters 580:2201-2206.
Verdugo, P., Orellana, M.V., Chin, W-C., Petersen, T.W., van den Eng, G., Benner, R., Hedges, J.I. (2008) Marine biopolymer self-assembly: Implications for carbon cycling in the ocean. Faraday DiscussionRoyal Society of Chemistry 139: 393-398
Verdugo, P. (2012) Marine gels. Rev. Mar. Sci. 4:375–400.
Verdugo P (2012) Supramolecular dynamics of mucus. Cold Spring Harb Perspect Med.10.11.01/cshperspect.a009597.
Verdugo, P. (2021) Biopolymer dynamics, gel formation, and carbon cycling in the ocean. Gels. 7:136-171
Verdugo, P., and C. Golborne (1981). Fiber optic light-scattering device for detecting ciliary activity in situ. Center for Bioengineering, University of Washington, Seattle, WA.
Verdugo, P., P.Y. Tam and C. Golborne (1982). Detection of sperm flagellation by micro-photodensitometry. Center for Bioengineering, University of Washington, Seattle, WA.
Verdugo, P. (1994). Remote triggering of drug release by X-ray uncaging-induced phase transition. Center for Bioengineering, University of Washington, Seattle, WA
Verdugo, P., Hoffman, AS. (1994) Stabilization of vaccines: A strategy to develop an “intelligent” polymer shield to protect viral and peptide/protein vaccines from thermal, enzymatic, or chemical degradation during storage and shipment. Dept. of Bioengineering, University of Washington, Seattle, WA