Philip A. Rea

Rea attended Gartree High School and Beauchamp College, Oadby, Leicester. He earned a BSc in Biological Sciences (First Class Honors) from the University of Sussex in 1978 and a DPhil in Plant Biochemistry from Magdalen College, Oxford in 1982. He was an MRC Research Fellow at the John Radcliffe Hospital, Oxford (1982–1984), a Merit Research Associate at McGill University (1984), and an AFRC Research Fellow at the University of York (1985–1987). Before joining the University of Pennsylvania in 1990, he was a Group Leader at Rothamsted Research.{{Cite web|url=https://lsm.upenn.edu/node/38|title=Dr. Philip A. Rea {{!}} Penn LSM|website=lsm.upenn.edu|access-date=2019-07-16}}

He began his pioneering studies at Rothamsted Research on plant vacuolar proton pumps and other key transporters involved in plant physiology.{{Cite web |date=2005-12-12 |title=New Penn Program Melds Business And Life Sciences |url=https://www.biospace.com/new-penn-program-melds-business-and-life-sciences |access-date=2025-05-24 |website=BioSpace |language=en-US}}

In 1990, Rea joined the University of Pennsylvania as a faculty member in the Department of Biology, where he spent most of his academic career. At Penn, Rea's research expanded to include both plant and animal models.{{Cite web |date=2021-09-27 |title=Biologist’s-Eye View |url=https://thepenngazette.com/biologists-eye-view/ |access-date=2025-05-24 |website=The Pennsylvania Gazette |language=en-US}}

A key turning point in Rea’s career came in 2005, when he co-founded the Roy and Diana Vagelos Program in Life Sciences & Management at the University of Pennsylvania alongside Mark V. Pauly. This unique interdisciplinary program combines the biological sciences with business education.{{cite web |title=Wharton Alumni Magazine |url=https://s3images.coroflot.com/user_files/individual_files/80582_WuDHgfI5UyTXMpmRYoRoXk5gn.pdf |website=The Wharton School of the University of Pennsylvania}}

Rea is known for his research on vacuolar proton (H⁺) pumps, ATP-binding cassette (ABC) transporters, and phytochelatin (PC) synthase. His early work on plant vacuolar H⁺-pumping ATPases led to the first definitive subunit composition of these enzymes and helped establish the concept of 'V-type ATPases' (Manolson et al., 1985).{{Cite journal|last1=Manolson|first1=M.F.|last2=Rea|first2=P.A.|date=1985|title=Identification of 2'(3')-O-(4-benzoylbenzoyl)adenosine-5'-triphosphate- and N,N'-dicyclohexylcarbodiimide-binding subunits of higher plant H+-translocating tonoplast ATPase|journal=J. Biol. Chem.|volume=260|issue=22 |pages=12273–12279|doi=10.1016/S0021-9258(17)39021-X|doi-access=free}} These studies, in turn, opened the way for biochemical and molecular investigations of these enzymes from many different sources, leading to recognition that the plant enzyme is just one example of a category of primary H⁺ pumps common to both plant and animal cells. Other contributions made by Rea in this specific area included elucidation of the gross topography of the V-ATPase, demonstrating that its organization is analogous to that of the F-type ATPases of 'energy coupling' membranes (Rea et al 1987a; Rea et al 1987b),{{Cite journal|last1=Rea|first1=P.A.|last2=Griffith|first2=C.J.|date=1987|title=Irreversible inhibition of H+-ATPase of higher plant tonoplast by chaotropic anions: evidence for peripheral location of nucleotide-binding subunits|journal=Biochim. Biophys. Acta|volume=904|pages=1–12|doi=10.1016/0005-2736(87)90080-0}}{{Cite journal|last1=Rea|first1=P.A.|last2=Griffith|first2=C.J.|date=1987|title=Purification of N,N'-dicyclohexylcarbodiimide binding proteolipid of higher plant vacuolar H+-translocating ATPase|journal=J. Biol. Chem.|volume=262|pages=14745–14752|doi=10.1016/S0021-9258(18)47858-1|doi-access=free}} and purification of the enzyme in its entirety to establish that the holoenzyme is a 12-15 subunit, complex comprising a peripheral, nucleotide-binding V1 sector and an intrinsic, H⁺-conductive V0 sector (Parry et al 1989).{{Cite journal|last1=Parry|first1=R.V.|last2=Turner|first2=J.C.|last3=Rea|first3=P.A.|date=1989|title=High purity preparations of higher plant vacuolar H+-ATPase reveal additional subunits: revised subunit composition|journal=J. Biol. Chem.|volume=264|issue=33|pages=20025–20032|doi=10.1016/S0021-9258(19)47213-X|pmid=2531142|doi-access=free}} Collectively, these discoveries provided some of the earliest evidence that V-type and F-type H⁺-ATPases are paralogous.

When Rea entered the field of vacuolar energetics, there were indications that plant vacuolar membranes also contained H⁺-pumping inorganic pyrophosphatases, which he confirmed by demonstrating that the membrane-associated vacuolar inorganic pyrophosphatase (V-PPase) of plants catalyzes pyrophosphate- (PPi-) energized electrogenic H⁺- translocation (Rea and Poole 1985){{Cite journal|last1=Rea|first1=P.A.|last2=Poole|first2=R.J.|date=1985|title=Proton-translocating inorganic pyrophosphatase in red beet (Beta vulgaris L.) tonoplast vesicles|journal=Plant Physiol.|volume=77|issue=1|pages=46–52|doi=10.1104/pp.77.1.46|pmid=16664026|pmc=1064454}} and is both functionally and chromatographically separable from the ATP-energized V-ATPase found on the same membrane (Rea and Poole 1986; Rea and Sanders 1987).{{Cite journal|last1=Rea|first1=P.A.|last2=Poole|first2=R.J.|date=1986|title=Chromatographic resolution of H+-translocating inorganic pyrophosphatase from H+-translocating ATPase of higher plant tonoplast|journal=Plant Physiol.|volume=81|issue=1|pages=126–129|doi=10.1104/pp.81.1.126|pmid=16664761|pmc=1075294}}{{Cite journal|last1=Rea|first1=P.A.|last2=Sanders|first2=D.|date=1987|title=Tonoplast energization: two H+ pumps, one membrane|journal=Plant Physiol.|volume=71|pages=131–141|doi=10.1111/j.1399-3054.1987.tb04630.x}} What then followed was a broad range of discoveries made by Rea's group concerned with defining the basic organization and core catalytic capabilities of the V-PPase. These included: (1) Purification of the pump, in parallel with identification of the major subunit through its substrate-protectable covalent modification with radiolabeled ligands (Britten et al 1989);{{Cite journal|last1=Britten|first1=C.J.|last2=Turner|first2=J.C.|last3=Rea|first3=P.A.|date=1989|title=Identification and purification of substrate binding subunit of higher plant H+-translocating inorganic pyrophosphatase|journal=FEBS Lett.|volume=256|issue=1–2|pages=200–206|doi=10.1016/0014-5793(89)81748-X|doi-access=free|bibcode=1989FEBSL.256..200B }} (2) Molecular cloning of the pump (AVP1) from Arabidopsis thaliana (Sarafian et al 1992), the very first V-PPase to be cloned from any source;{{Cite journal|last1=Sarafian|first1=V.|last2=Kim|first2=Y.|last3=Poole|first3=R.J.|last4=Rea|first4=P.A.|date=1992|title=Molecular cloning and sequence of cDNA encoding the pyrophosphate-energized vacuolar membrane proton pump (H+-PPase) of Arabidopsis thaliana|journal=Proc. Natl. Acad. Sci.|volume=89|issue=5|pages=1775–1779|doi=10.1073/pnas.89.5.1775|pmid=1311852|pmc=48535|doi-access=free}} (3) In vitro reconstitution of the transport activity of the purified pump (Britten et al 1992);{{Cite journal|last1=Britten|first1=C.J|last2=Zhen|first2=R.-G.|last3=Kim|first3=E.J.|last4=Rea|first4=P.A.|date=1992|title=Reconstitution of transport function of vacuolar H+-translocating inorganic pyrophosphatase|journal=J. Biol. Chem.|volume=267|issue=30|pages=21850–21855|doi=10.1016/S0021-9258(19)36690-6|pmid=1328246|doi-access=free}} (4) Definition of the pump as a new category of ion translocase, together with speculations (which were subsequently confirmed) that the D[X]₇KXE motif common to both vacuolar and soluble PPases participates directly in catalysis (Rea et al 1992);{{Cite journal|last1=Rea|first1=P.A.|last2=Kim|last3=Sarafian|last4=Poole|last5=Sanders|last6=Davies|date=1992|title=Vacuolar H+-translocating inorganic pyrophosphatase: a new category of ion translocase|journal=Trends Biochem. Sci.|volume=17|issue=9|pages=348–353|doi=10.1016/0968-0004(92)90313-X|pmid=1329278|doi-access=free}} (5) Heterologous expression of the pump from Arabidopsis in yeast (Saccharomyces cerevisiae), to demonstrate that the 'substrate-binding subunit' alone is sufficient for PPi-dependent H⁺-translocation (Kim et al 1994);{{Cite journal|last1=Kim|first1=E.J.|last2=Zhen|first2=R.-G.|last3=Rea|first3=P.A.|date=1994|title=Heterologous expression of plant vacuolar pyrophosphatase in yeast demonstrates sufficiency of substrate-binding subunit for proton transport|journal=Proc. Natl. Acad. Sci. USA|volume=91|issue=13|pages=6128–6132|doi=10.1073/pnas.91.13.6128|pmid=8016125|pmc=44151|bibcode=1994PNAS...91.6128K|doi-access=free}} (6) Identification of aminomethylenediphosphonate (AMDP) as a potent type-specific inhibitor of the pump from both plant and photosynthetic bacterial sources (Baykov et al 1993; Zhen et al 1994);{{Cite journal|last1=Baykov|first1=A.A.|last2=Dubnova|last3=Zhen|last4=Bakuleva|last5=Evtushenko|last6=Rea|date=1993|title=Differential sensitivity of membrane-associated pyrophosphatases to diphosphonates and fluoride delineates two classes of enzyme|journal=FEBS Lett.|volume=317|issue=2|pages=199–202|doi=10.1016/0014-5793(93)80169-U|pmid=8392953|s2cid=40264742}}{{Cite journal|last1=Zhen|first1=R.-G.|last2=Baykov|last3=Bakuleva|last4=Rea|date=1994|title=Aminomethylenediphosphonate: a potent type-specific inhibitor of V-type H+-pyrophosphatases in plants and phototrophic bacteria|journal=Plant Physiol|volume=104|issue=1|pages=153–159|doi=10.1104/pp.104.1.153|pmid=12232069|pmc=159173}} (7) Protein chemical identification of the maleimide-reactive domain of the pump and modeling of the topology of the C-terminal half of the molecule by peptide mapping and the deployment of both membrane-permeant and membrane-impermeant maleimides (Zhen et al 1994);{{Cite journal|last1=Zhen|first1=R.-G.|last2=Kim|first2=E.J.|last3=Rea|first3=P.A.|date=1994|title=Localization of cytosolically oriented maleimide-reactive domain of vacuolar H+-pyrophosphatase|journal=J. Biol. Chem.|volume=269|issue=37|pages=23342–23350|doi=10.1016/S0021-9258(17)31659-9|pmid=8083239|doi-access=free}} (8) Identification of acidic residues required for coupling PPi hydrolysis to H⁺-translocation by the pump (Zhen et al 1997);{{Cite journal|last1=Zhen|first1=R.-G.|last2=Kim|first2=E.J.|last3=Rea|first3=P.A.|date=1997|title=Acidic residues necessary for pyrophosphate-energized pumping and inhibition of the vacuolar H+-pyrophosphatase by N,N'-dicyclohexylcarbodiimide|journal=J. Biol. Chem.|volume=272|issue=35|pages=22340–22348|doi=10.1074/jbc.272.35.22340|pmid=9268385|doi-access=free}} (9) Isolation and functional characterization of a thermostable sequence-divergent homolog from the extremophilic archaeon Pyrobaculum aerophilum (Drozdowicz et al 1999);{{Cite journal|last1=Drozdowicz|first1=Y.M.|last2=Lu|first2=Y.-P.|last3=Patel|first3=V.|last4=Fitz-Gibbon|first4=S.|last5=Miller|first5=J.|last6=Rea|first6=P.A.|date=1999|title=PVP, a thermostable vacuolar-type pyrophosphate-dependent pump from the archaeon Pyrobaculum aerophilum: implications for the origins of pyrophosphate-energized pumps|journal=FEBS Lett.|volume=460|issue=3|pages=502–512|doi=10.1016/S0014-5793(99)01404-0|pmid=10556526|s2cid=44664144|doi-access=free}} (10) Molecular identification, isolation and functional characterization of a type II (K⁺-independent) version of the pump from Arabidopsis and the first demonstration that members of this pump category fall into two distinct classes (Drozdowicz et al 2000);{{Cite journal|last1=Drozdowicz|first1=Y.M.|last2=Kissinger|first2=J.C.|last3=Rea|first3=P.A.|date=2000|title=AVP2, a sequence-divergent, monovalent cation-insensitive H+-translocating inorganic pyrophosphatase from Arabidopsis thaliana|journal=Plant Physiol.|volume=123|issue=1|pages=353–362|doi=10.1104/pp.123.1.353|pmid=10806252|pmc=59009}} (11) Comparative genomic analyses of V-PPases to disclose examples of this pump category in all three domains of life and confirm the notion of two paralogous series, typified by the type I and type II enzymes (Drozdowicz et al 2001);{{Cite journal|last1=Drozdowicz|first1=Y.M.|last2=Rea|first2=P.A.|date=2001|title=Vacuolar H+-pyrophosphatases: from the evolutionary backwaters into the mainstream|journal=Trends Plant Sci.|volume=6|issue=5|pages=206–211|doi=10.1016/S1360-1385(01)01923-9|pmid=11335173|bibcode=2001TPS.....6..206D }} (12) Molecular isolation, functional characterization and cellular localization of a type I pump from the parasitic protist responsible for toxoplasmosis, Toxoplasma gondii (Drozdowicz et al 2002).{{Cite journal|last1=Drozdowicz|first1=Y.M.|last2=Shaw|first2=M.|last3=Nishi|first3=M.|last4=Striepen|first4=B.|last5=Liwinski|first5=H.A.|last6=Roos|first6=D.S.|last7=Rea|first7=P.A.|date=2003|title=Isolation and functional characterization of TgVP1, a type I vacuolar H+-translocating pyrophosphatase from Toxoplasma gondii: the dynamics of its subcellular localization and the cellular effects of a diphosphonate|journal=J. Biol. Chem.|volume=278|issue=2|pages=1075–1085|doi=10.1074/jbc.M209436200|pmid=12411435|doi-access=free}}

Rea's research on ABC transporters has largely focused on members of this superfamily from plant and fungal sources. His group, in collaboration with Dr. Dennis J. Thiele's group (then at the University of Michigan) molecularly and biochemically defined yeast cadmium factor 1 (YCF1), a yeast (S. cerevisiae) MRP- (ABCC-) type ABC transporter to show that it catalyzes the ATP-energized vacuolar uptake of glutathione- (GS-) conjugates (Li et al 1996).{{Cite journal|last1=Li|first1=Z.-S.|last2=Szcypka|first2=M.|last3=Thiele|first3=D.J.|last4=Rea|first4=P.A.|date=1996|title=The yeast cadmium factor protein (YCF1) is a vacuolar glutathione S-conjugate transporter|journal=J. Biol. Chem.|volume=271|issue=11|pages=6509–6517|doi=10.1074/jbc.271.11.6509|pmid=8626454|doi-access=free}} This resulted in the discovery of a new pathway for heavy metal detoxification: YCF1-catalyzed vacuolar sequestration of GS-heavy metal complexes, as exemplified by the bis(glutathionato)cadmium and tris(glutathionato)arsenic complexes formed between glutathione and cadmium (Li et al 1997){{Cite journal|last1=Li|first1=Z.-S.|last2=Lu|first2=Y.-P.|last3=Thiele|first3=D.J.|last4=Rea|first4=P.A.|date=1997|title=A new pathway for vacuolar cadmium sequestration in Saccharomyces cerevisiae: YCF1-mediated transport of bis(glutathionato)cadmium|journal=Proc. Natl. Acad. Sci.|volume=94|issue=1|pages=42–47|doi=10.1073/pnas.94.1.42|pmid=8990158|pmc=19233|doi-access=free}} and arsenic, respectively (Ghosh et al 1999).{{Cite journal|last1=Ghosh|first1=M.|last2=Shen|first2=J.|last3=Rosen|first3=B.P.|date=1999|title=Pathways of As(III) detoxification in Saccharomyces cerevisiae|journal=Proc. Natl. Acad. Sci. USA|volume=96|issue=9|pages=5001–5006|doi=10.1073/pnas.96.9.5001|pmid=10220408|pmc=21806|bibcode=1999PNAS...96.5001G|doi-access=free}} Using tools developed in the course of their studies of YCF1 for parallel screens for similar functionalities from plant sources, Rea's group was the first to both functionally and molecularly define an ABC transporter from a vascular plant (Arabidopsis thaliana) (Lu et al 1997; Lu et al 1998).{{Cite journal|last1=Lu|first1=Y.-P.|last2=Li|first2=Z.-S.|last3=Rea|first3=P.A.|date=1997|title=AtMRP1 gene of Arabidopsis thaliana encodes a glutathione S-conjugate pump: isolation and functional definition of a plant ATP binding cassette transporter gene|journal=Proc. Natl. Acad. Sci. USA|volume=94|issue=15|pages=8243–8248|doi=10.1073/pnas.94.15.8243|pmid=9223346|pmc=21588|doi-access=free}}{{Cite journal|last1=Lu|first1=Y.-P.|last2=Li|first2=Z.-S.|last3=Drozdowicz|first3=Y.M.|last4=Hortensteiner|first4=S.|last5=Martinoia|first5=E.|last6=Rea|first6=P.A.|date=1998|title=AtMRP2, an Arabidopsis ATP-binding cassette transporter able to transport glutathione S-conjugates and chlorophyll catabolites: functional comparisons with AtMRP1|journal=Plant Cell|volume=10|issue=2|pages=267–82|doi=10.1105/tpc.10.2.267|pmid=9490749|pmc=143980}} The ABC transporters identified, AtMRP1 and AtMRP2 (alias AtABCC1 and AtABCC2), were shown to be involved in the ATP-energized vacuolar sequestration and detoxification of both endogenous and exogenous toxins, largely amphipathic anions primarily in the form of GS-conjugates (Lu et al 1997; 1998; Liu et al 2001).{{Cite journal|last1=Lu|first1=Y.-P.|last2=Li|first2=Z.-G.|last3=Rea|first3=P.A.|date=1997|title=AtMRP1 gene of Arabidopsis thaliana encodes a glutathione S-conjugate pump: isolation and functional definition of a plant ATP binding cassette transporter gene|journal=Proc. Natl. Acad. Sci. USA|volume=94|issue=15|pages=8243–8248|doi=10.1073/pnas.94.15.8243|pmid=9223346|pmc=21588|doi-access=free}}{{Cite journal|last1=Lu|first1=Y.-P.|last2=Li|first2=Z.-S.|last3=Drozdowicz|first3=Y.M.|last4=Hortensteiner|first4=S.|last5=Martinoia|first5=E.|last6=Rea|first6=P.A.|date=1998|title=AtMRP2, an Arabidopsis ATP-binding cassette transporter able to transport glutathione S-conjugates and chlorophyll catabolites: functional comparisons with AtMRP1|journal=Plant Cell|volume=10|issue=2|pages=267–82|doi=10.1105/tpc.10.2.267|pmid=9490749|pmc=143980}}{{Cite journal|last1=Liu|first1=G.|last2=Sánchez-Fernández|first2=R.|last3=Rea|first3=P.A.|date=2001|title=Enhanced multispecificity of vacuolar membrane-localized ABC transporter AtMRP2|journal=J. Biol. Chem.|volume=276|issue=12|pages=8648–8656|doi=10.1074/jbc.M009690200|pmid=11115509|doi-access=free}} In compiling the first complete inventory of ABC proteins from a plant source, Rea and colleagues established that these organisms allocate a substantial fraction of their genomes to members of this protein family. The genome of Arabidopsis thaliana, for instance, contains more than 130 ORFs for these proteins of which more than 100 are transmembrane proteins (Sánchez-Fernández et al 2001; Rea 2007).{{Cite journal|last1=Sánchez-Fernández|first1=R.|last2=Davies|first2=T.G.E.|last3=Coleman|first3=J.O.D|last4=Rea|first4=P.A.|date=2001|title=The Arabidopsis thaliana ABC protein superfamily: a complete inventory|journal=J. Biol. Chem.|volume=276|issue=32|pages=30231–30244|doi=10.1074/jbc.M103104200|pmid=11346655|doi-access=free}}{{Cite journal|last=Rea|first=P.A.|date=2007|title=Plant ATP-binding cassette transporters|journal=Annual Review of Plant Biology|volume=58|pages=347–375|doi=10.1146/annurev.arplant.57.032905.105406|pmid=17263663}} This gene count far exceeds that of humans and other animals.

It was Rea's group (Vatamaniuk et al 1999){{Cite journal|last1=Vatamaniuk|first1=O.K.|last2=Mari|first2=S.|last3=Lu|first3=Y.-P.|last4=Rea|first4=P.A.|date=1999|title=AtPCS1, a phytochelatin synthase from Arabidopsis: isolation and in vitro reconstitution|journal=Proc. Natl. Acad. Sci.|volume=96|issue=12|pages=7110–7115|doi=10.1073/pnas.96.12.7110|pmid=10359847|pmc=22073|bibcode=1999PNAS...96.7110V|doi-access=free}} and two others (Clemens et al 1999; Ha et al 1999){{Cite journal|last1=Clemens|first1=S.|last2=Kim|first2=E.J.|last3=Neumann|first3=D.|last4=Schroeder|first4=J.I.|date=1999|title=Tolerance to toxic metals by a gene family of phytochelatin synthases from plants and yeast|journal=EMBO J.|volume=18|issue=12|pages=3325–3333|doi=10.1093/emboj/18.12.3325|pmid=10369673|pmc=1171413}}{{Cite journal|last1=Ha|first1=S.B.|last2=Smith|first2=A.P.|last3=Howden|first3=R.|last4=Dietrich|first4=W.M.|last5=Bugg|first5=S.|last6=O'Connell|first6=M.J.|last7=Goldsbrough|first7=P.B.|last8=Cobbett|first8=C.S.|date=1999|title=Phytochelatin synthase genes from Arabidopsis and the yeast Schizosaccharomyces pombe.|journal=Plant Cell|volume=11|issue=6|pages=1153–1164|doi=10.1105/tpc.11.6.1153|pmid=10368185|pmc=144235}} that simultaneously and independently first identified genes encoding the enzyme, phytochelatin (PC) synthase responsible for the synthesis of phytochelatins (PCs) by transfer of a γ-Glu-Cys unit from one thiol peptide to another or to a previously-synthesized PC for the detoxification of heavy metals. Thereafter, he and his colleagues: (1) Defined the basic catalytic mechanism and mode of activation of the enzyme by heavy metals by establishing that blocked thiols are sufficient for PC synthase-catalyzed transpeptidation of glutathione (GSH) and related thiol peptides via a substituted enzyme mechanism (Vatamanaiuk et al 2000);{{Cite journal|last1=Vatamaniuk|first1=O.K.|last2=Mari|first2=S.|last3=Lu|first3=Y.-P.|last4=Rea|first4=P.A.|date=2000|title=Mechanism of heavy metal activation of phytochelatin (PC) synthase: blocked thiols are sufficient for PC synthase-catalyzed transpeptidation of glutathione and related thiol peptides|journal=J. Biol. Chem.|volume=275|issue=40|pages=31451–31459|doi=10.1074/jbc.M002997200|pmid=10807919|doi-access=free}} (2) Determined that PC synthase is a dipeptidyl transferase that forms an enzyme γ-Glu-Cys acyl-intermediate during catalysis (Vatamaniuk et al (2004);{{Cite journal|last1=Vatamaniuk|first1=O.K.|last2=Mari|first2=S.|last3=Lang|first3=A.|last4=Chalasani|first4=S.|last5=Demkiv|first5=L.O.|last6=Rea|first6=P.A.|date=2004|title=Phytochelatin synthase, a dipeptidyl transferase that undergoes multisite acylation with γ-glutamylcysteine during catalysis. Stoichiometry and site-directed mutagenic analysis of AtPCS1-catalyzed phytochelatin synthesis|journal=J. Biol. Chem.|volume=279|issue=21|pages=22449–22460|doi=10.1074/jbc.M313142200|pmid=15004013|doi-access=free}} (3) Demonstrated that PC synthase is a distant cousin of papain-like cysteine proteases and deploys a Cys-His-Asp catalytic triad to catalyze the dipeptidyl transferase reaction through the formation of a γ-Glu-Cys-thioester intermediate (Rea et al 2004; Romanyuk et al 2006);{{Cite journal|last1=Rea|first1=P.A.|last2=Vatamaniuk|first2=O.K.|last3=Rigden|first3=D.J.|date=2004|title=Weeds, worms, and more. Papain's long-lost cousin, phytochelatin synthase|journal=Plant Physiol|volume=136|issue=1|pages=2463–2474|doi=10.1104/pp.104.048579|pmid=15375203|pmc=523314}}{{Cite journal|last1=Romanyuk|first1=N.D.|last2=Rigden|first2=D.J.|last3=Vatamaniuk|first3=O.K.|last4=Lang|first4=A.|last5=Cahoon|first5=R.E.|last6=Jez|first6=J.M.|last7=Rea|first7=P.A.|date=2006|title=Mutagenic definition of papain-like catalytic triad, sufficiency of N-terminal domain for single-site core catalytic enzyme acylation and C-terminal domain for augmentative metal activation of an eukaryotic phytochelatin synthase|journal=Plant Physiol.|volume=141|issue=3|pages=858–869|doi=10.1104/pp.106.082131|pmid=16714405|pmc=1489916}} results that were subsequently independently confirmed by crystallographic analyses of a PC synthase homolog from the cyanobacterium Nostoc sp. PCC 7120 (Vivares et al 2005; Rea 2006).{{Cite journal|last1=Vivares|first1=D.|last2=Arnoux|first2=P.|last3=Pignol|first3=D.|date=2005|title=A papain-like enzyme at work: Native and acyl–enzyme intermediate structures in phytochelatin synthesis|journal=Proc. Natl. Acad. Sci.|volume=102|issue=52|pages=18848–18853|doi=10.1073/pnas.0505833102|pmid=16339904|pmc=1310510|bibcode=2005PNAS..10218848V|doi-access=free}}{{Cite journal|last=Rea|first=P.A.|date=2006|title=Phytochelatin synthase, papain's cousin, in stereo|journal=Proc. Natl. Acad. Sci.|volume=103|issue=3|pages=507–508|doi=10.1073/pnas.0509971102|pmid=16407124|pmc=1334667|bibcode=2006PNAS..103..507R|doi-access=free}} One of the most surprising findings to come from the cloning of PC synthase and its equivalents from other plants and the fungus Schizosaccharomyces pombe was the discovery of a similar gene in an animal. Routine database searches disclosed a homologous single-copy gene (ce-pcs-1) in the genome of the nematode Caenorhabditis elegans, which Rea and colleagues took a step further to demonstrate that CePCS1 is a PC synthase, and that targeted suppression of ce-pcs-1 by the double-stranded RNA interference (RNAi) technique confers a cad1-like heavy metal-hypersensitive phenotype on C. elegans (Vatamaniuk et al 2001; Vatamaniuk et al 2002).{{Cite journal|last1=Vatamaniuk|first1=O.K.|last2=Bucher|first2=E.A.|last3=Ward|first3=J.T.|last4=Rea|first4=P.A.|date=2001|title=A new pathway for heavy metal detoxification in animals: phytochelatin synthase is required for cadmium tolerance in Caenorhabditis elegans|journal=J. Biol. Chem.|volume=276|issue=24|pages=20817–20820|doi=10.1074/jbc.C100152200|pmid=11313333|doi-access=free}}{{Cite journal|last1=Vatamaniuk|first1=O.K.|last2=Bucher|first2=E.A.|last3=Rea|first3=P.A.|date=2002|title=Worms take the 'phyto' out of 'phytochelatins'|journal=Trends Biotechnol|volume=20|issue=2|pages=61–64|doi=10.1016/S0167-7799(01)01873-X|pmid=11814595}} While other gene products had been inferred to contribute to heavy metal tolerance in C. elegans, CePCS1 was the first for which a firm biochemical basis for the effects seen at the level of the whole organism was established.

Rea's current research, which owes its origins to his leadership of the Vagelos Program in Life Sciences & Management, focuses on case studies of the interface between life sciences research and its implementation; the difficult transition from discovery in the laboratory to success in the market and/or toward the expansion of humanitarian efforts. Examples of such case studies are 'Statins: from fungus to pharma,'{{Cite journal|last=Rea|first=P.A.|date=2008|title=Statins: from fungus to pharma|journal=American Scientist|volume=96|issue=5|pages=408–415|doi=10.1511/2008.74.408}} 'Ivermectin and river blindness,'{{Cite journal|last1=Rea|first1=P.A.|last2=Zhang|first2=V.|last3=Baras|first3=Y.S.|date=2010|title=Ivermectin and river blindness|journal=American Scientist|volume=98|pages=294–303}} 'Can skinny fat beat obesity?',{{Cite journal|last1=Rea|first1=P.A.|last2=Yin|first2=P.|last3=Zahalka|first3=R.|date=2014|title=Can skinny fat beat obesity?|journal=American Scientist|volume=102|issue=4|pages=272–279|doi=10.1511/2014.109.272}} and 'Metformin: out of the backwaters and into the mainstream';{{Cite journal|last1=Rea|first1=P.A.|last2=Tien|first2=A.Y.|date=2017|title=Metformin: out of backwaters and into the mainstream|journal=American Scientist|volume=105|issue=2|pages=102–111|doi=10.1511/2017.105.2.102}} four articles aimed primarily at the educated non-specialist. The book Managing Discovery: Harnessing Creativity to Drive Biomedical Innovation (2018), coauthored with Mark V. Pauly and Lawton R. Burns, which is an extension of this research effort, addresses the link between life sciences discoveries and their dependence on the investor-driven market system. It looks at how the science actually played out through the interplay of personalities, the cultures within and between academic and corporate entities, and the significance of serendipity not as a mysterious phenomenon but one intrinsic to the successes and failures of the experimental approach. With newly aggregated data and case studies, the fundamental economic underpinnings of investor-driven discovery management are considered, not as an obstacle or deficiency, but as the only means by which scientists and managers can navigate the unknowable to discover new products.

Rea has received the President's Medal from the Society for Experimental Biology, UK for pioneering investigations of primary proton pumps (1990), a Cozzarelli Prize from the National Academy of Sciences, USA for coauthorship of a paper of scientific excellence and originality (2010), and election as a Fellow of the American Association for the Advancement of Science for research discoveries on the membrane transport and detoxification of xenobiotics, and for distinguished accomplishments and creativity in science education (2013). His awards and honors in the educational sector include an Ira H. Abrams Memorial Award for Distinguished Teaching (the College of Arts and Sciences' highest teaching honor) (2009), a Christian R. and Mary F. Lindback Award for Distinguished Teaching (the University's highest teaching honor) (2014), the Department of Biology's Award for Excellence in Teaching (1996, 2005, 2013, 2019), and a Wharton Teaching Excellence Award (2019).{{Cite web |last=Feiner |first=Lauren |title=The Daily Pennsylvanian {{!}} The University of Pennsylvania's independent student news organization |url=https://www.thedp.com/article/2014/01/philip_a_rea_wins_aaas_fellowship |access-date=2025-05-24 |website=www.thedp.com |language=en-us}}

Rea was awarded an honorary Doctorate of Science (D.Sc.) by the University of Oxford, UK (2020) in recognition of his seminal biochemical research, and dedication and devotion to teaching, science-communication, and mentorship.{{Cite web |title=Dr. Philip A. Rea awarded a Doctorate of Science |url=https://www.bio.upenn.edu/node/7174 |website=University of Pennsylvania}}

In 2025, Rea was awarded the Neal Award for excellence in scientific journalism.{{Cite web |title=Professor Philip A. Rea is this year’s winner of the Neal Award for scientific journalism |url=https://www.bio.upenn.edu/node/8986 |website=University of Pennsylvania}}

Rea is the author of over 130 papers and commentaries,{{Cite web|url=https://scholar.google.com/citations?user=1s3GeggAAAAJ&hl=en|title=Philip A. Rea - Google Scholar Citations|website=scholar.google.com|access-date=2019-08-16}} and the author of two books, Fall (2004) and Managing Discovery: Harnessing Creativity to Drive Biomedical Innovation (2018).

Fall (2004), a photo-book for which Rea wrote the text, is a "hyper-macroscopic analysis of the color transformations characteristic of tree foliage in the Northeastern United States autumn...[featuring] vivid and brilliant images."{{Cite book|title=Fall : photographs|last=Griffith|first=Christopher|date=2004|publisher=Powerhouse Books|others=Whitman, Walt, 1819-1892., Rea, Philip A.|isbn=9781576872260|edition=1st|location=New York|oclc=54865347}} This book was a joint project with Rea's former biochemistry mentee, Christopher Griffith, who is now a professional photographer.{{Cite web|url=http://www.christophergriffith.com|title=LANDING|website=CHRISTOPHERGRIFFITH|language=en-US|access-date=2017-12-15}}

Managing Discovery: Harnessing Creativity to Drive Biomedical Innovation (2018),{{Cite book|title=Managing discovery in the life sciences: harnessing creativity to drive biomedical innovation|last1=Rea|first1=Philip A.|last2=Pauly|first2=Mark V.|last3=Burns|first3=Lawton R.|publisher=Cambridge University Press|year=2018|isbn=9781107577305|location=Cambridge, United Kingdom|oclc=1002043963}} coauthored with Mark V. Pauly and Lawton R. Burns, addresses the link between life sciences discoveries and their dependence on the investor-driven market system through in-depth considerations of the challenges that both scientists and managers must face in the pharmaceutical and medical device industries.

Other publications, a selection:

• Rea, P.A. (2024) Gliflozins for diabetes: from bark to bench to bedside. American Scientist, 112: 360-367
• Rea, P.A. (2023) Wie Glyphosat die Welt eroberte. Spektrum der Wissenschaft, 56-63.

• Rea, P.A. (2022) How glyphosate cropped up. American Scientist, 110: 170-177.
• Rea, P.A. (2020) Phytochelatin Synthase. In: Encyclopedia of Life Sciences (eLS). John Wiley & Sons, Ltd: Chichester, 1-15. DOI: 10.1002/9780470015902.a0028220.
• Rea, P.A. (2018) Plant Vacuoles. In: Encyclopedia of Life Sciences (eLS). John Wiley & Sons, Ltd: Chichester, 1-14. DOI: 10.1002/9780470015902.a0001675.pub3.
• Cahoon, R.E., Lutke, W.K., Cameron, J.C., Chen, S., Lee, S.G., Rivard, R.S., Rea, P.A., Jez, J.M. (2015) Adaptive engineering of phytochelatin-based heavy metal tolerance. J. Biol. Chem., 290: 17321-17330.
• Rea, P.A., Yin, P., Zahalka, R. (2015) Mit beigem Fett gegen Übergewicht? Spektrum der Wissenschaft, 26-32.
• Rea, P.A. (2012) Phytochelatin synthase: of a protease a peptide polymerase made. Physiol. Plant., 145: 154-164.
• Park, J., Song, W.-J., Mendoza-Cózat, D.G., Suter-Grotemeyer, M., Shim, D., Hörtensteiner, S., Geisler, M., Rea, P.A., Rentsch, D., Schroeder, J.I., Lee, Y., Martinoia, E. (2010) Arsenic tolerance in Arabidopsis is mediated by two ABCC-type phytochelatin transporters. Proc. Natl. Acad. Sci. USA, 107: 21187-21192.
• Rea, P.A. (2009) Talk about teaching and learning: The kick is in finding out stuff about stuff and sharing it with others. Almanac, 55: 8.
• Rea, P.A. (2009) Les statines: de la moisissure aux médicaments. Pour la science, N°379, Mai 2009.

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• {{official|https://www.bio.upenn.edu/people/philip-rea}}

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Category:University of Pennsylvania faculty

Category:University of Pennsylvania Department of Biology faculty

Category:Alumni of the University of Sussex

Category:1957 births

Category:Living people

Category:Alumni of Magdalen College, Oxford

Category:English biochemists

Category:People from Wolverhampton