Remembering Paul Kelly, PhD (1943 – 2018)

It is with great sadness that we learned that Professor Paul Kelly passed away on Wednesday November 28, 2018.

Paul was an internationally well-known endocrinologist. After receiving his PhD in endocrinology and reproductive physiology from the University of Wisconsin in 1972, Paul went to Canada to do his post-doctoral training in the laboratories of the renowned Professors Henry Friesen (McGill University and University of Manitoba) and Fernand Labrie (Laval University). In 1975, at Laval University, he joined the group in ‘Molecular Endocrinology’ of the Medical Research Council of Canada, and, in 1983, he became a full professor in the Department of Medicine of McGill University where he created the Laboratory of Molecular Endocrinology that he directed until 1991.

At this time, he decided to move to France, specifically to the Faculty of Medicine Necker (University of Paris Descartes), where he created the Inserm Unit 344 that he directed for 15 years as a senior director of research at Inserm followed by an appointment as a University Hospital professor (1993).  During this time, Paul played a key role in a project to bring together several laboratories on the Necker campus, and, in 2007, succeeded in creating the Research Center ‘Growth and Signaling’ (Inserm Unit 845) that he directed until 2010.  This structure has become a department of the present Institute Necker Enfants Malades (INEM, Inserm U1151) of which Paul was a member until 2014 as a professor emeritus.

Endocrinology has lost a leader and a creative contributor whose life is a shining example of the triumph of the resilience of the human spirit in the face of crippling adversity.

Besides science and research, Paul also contributed significantly to the evolution of the Necker campus at the critical turn of the 21^st Century; he was the director of the “Institut Fédératif de Recherches” between 2000 and 2010. Paul was a visionary; his actions stimulated the emergence of several technologic core facilities. Despite numerous obstacles, Paul persevered in his objective to contribute to this structuring of the Necker campus and today, the entire research community of Necker is indebted to him.

During his career, Paul made fundamental contributions to the field of research on the hormone prolactin.  After making significant advances on the actions of prolactin at Laval University, Paul and his team at McGill University made an internationally acclaimed breakthrough by cloning the prolactin receptor (Cell, 1988).  This result constituted the basis of the work that he continued at the Faculty of Medicine at Necker to elucidate the molecular mechanisms of action of prolactin and, using a prolactin receptor-deficient mouse model, the complex pathophysiology of this pleiotropic hormone.

Paul had a strong involvement in editorial activities and served as editor for numerous leading journals in the field of endocrinology. He was an associate editor of the Endocrine Society journal Endocrinology from 1990 to 1992 under editor-in-chief Michael Conn. Together with Professor E.E. Baulieu, Paul edited the famous textbook Hormones: From Molecules to Disease (Hermann, Paris and Chapman-Hall, New York, 1990). He was the Chairman for Basic Research of the 82^nd Endocrine Society meeting (ENDO) in 2000 and chaired the Gordon Research Conference on Prolactin in 2002. Paul was member of nine distinguished societies. He published over 400 peer-reviewed articles and was a recipient of several prestigious honors and awards, including the Chaire in Molecular Endocrinology of the Fondation de France, the Endocrine Society’s Gerald D. Aurbach Award, and the French Ordre national du mérite.

During his exceptional scientific career, Paul remained humble. Accessible, always turned towards others, he was instrumental for the early career of a great number of young scientists who, today, are infinitely grateful. He was also an exceptional teacher.

We will remember Paul Kelly as a leading scientist in his field, a mentor, a federator and, maybe above all, a man of incomparable kindness and rare humanism.

Henry Friesen says: “Today I recall an earlier period both at McGill and the University of Manitoba when the terra incognito of the domains of prolactin and growth hormone receptors were beginning to be explored. And of course Paul Kelly, Bob Shiu, and Michael Waters were pioneers and trailblazers in the journey of discovery in my lab at that time. But it was Paul Kelly who singlehandedly with his team pursued the scientific quest using ever more sophisticated tools to define the mysteries and mechanisms of the prolactin receptor-ligand hormone interactions and the post receptor signals. It was a monumental achievement made even more heroic as the advances and progress occurred despite the intrusive health challenges he faced over an extended period. Endocrinology has lost a leader and a creative contributor whose life is a shining example of the triumph of the resilience of the human spirit in the face of crippling adversity.”

We will remember Paul Kelly as a leading scientist in his field, a mentor, a federator and, maybe above all, a man of incomparable kindness and rare humanism.

 

Author affiliations: 1. Inserm U1151/Institut Necker Enfants Malades, University Paris Descartes, Paris, France; 2. Departments of Medicine, Pharmacology and Obstetrics & Gynecology, McGill University, Montreal, QC, Canada; 3. Institut Fédératif de Recherche Necker-Enfants Malades (IRNEM), Paris, France; 4. AP-HP, IE3M, Hôpital Pitié-Salpêtrière, Department of Endocrinology and Reproductive Medicine, Paris, France; and 5. University of Manitoba Winnipeg, MB, Canada.

Selected References

1. Shiu RP, Kelly PA, Friesen HG. Radioreceptor assay for prolactin and other lactogenic hormones. Science 1973; 180:968-971
2. Kelly PA, Robertson HA, Friesen HG. Temporal pattern of placental lactogen and progesterone secretion in sheep. Nature 1974; 248:435-437
3. Posner BI, Kelly PA, Friesen HG. Induction of a lactogenic receptor in rat liver: influence of estrogen and the pituitary. Proc Natl Acad Sci U S A 1974; 71:2407-2410
4. Posner BI, Kelly PA, Friesen HG. Prolactin receptors in rat liver: possible induction by prolactin. Science 1975; 188:57-59
5. Djiane J, Houdebine LM, Kelly PA. Prolactin-like activity of anti-prolactin receptor antibodies on casein and DNA synthesis in the mammary gland. Proc Natl Acad Sci U S A 1981; 78:7445-7448
6. Turcot-Lemay L, Kelly PA. Prolactin receptors in human breast tumors. J Natl Cancer Inst 1982; 68:381-383
7. Gandilhon P, Melancon R, Djiane J, Kelly PA. N-nitroso-N-methylurea-induced mammary tumors in the rat: role of prolactin and a prolactin-lowering drug. J Natl Cancer Inst 1983; 70:105-109
8. Houdebine LM, Djiane J, Kelly PA. Retraction: Prolactin induces release of a factor from membranes capable of stimulating beta-casein gene transcription in isolated mammary cell nuclei. Proc Natl Acad Sci U S A 1985; 82:3062
9. Boutin JM, Jolicoeur C, Okamura H, Gagnon J, Edery M, Shirota M, Banville D, Dusanter-Fourt I, Djiane J, Kelly PA. Cloning and expression of the rat prolactin receptor, a member of the growth hormone/prolactin receptor gene family. Cell 1988; 53:69-77
10. Kelly PA, Djiane J, Postel-Vinay MC, Edery M. The prolactin/growth hormone receptor family. Endocr Rev 1991; 12:235-251
11. Lebrun JJ, Ali S, Goffin V, Ullrich A, Kelly PA. A single phosphotyrosine residue of the prolactin receptor is responsible for activation of gene transcription. Proc Natl Acad Sci U S A 1995; 92:4031-4035
12. Sandra O, Sohm F, de Luze A, Prunet P, Edery M, Kelly PA. Expression cloning of a cDNA encoding a fish prolactin receptor. Proc Natl Acad Sci U S A 1995; 92:6037-6041
13. Freemark M, Driscoll P, Maaskant R, Petryk A, Kelly PA. Ontogenesis of prolactin receptors in the human fetus in early gestation. Implications for tissue differentiation and development. J Clin Invest 1997; 99:1107-1117
14. Ormandy CJ, Camus A, Barra J, Damotte D, Lucas B, Buteau H, Edery M, Brousse N, Babinet C, Binart N, Kelly PA. Null mutation of the prolactin receptor gene produces multiple reproductive defects in the mouse. Genes Dev 1997; 11:167-178
15. Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA. Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev 1998; 19:225-268
16. Touraine P, Martini JF, Zafrani B, Durand JC, Labaille F, Malet C, Nicolas A, Trivin C, Postel-Vinay MC, Kuttenn F, Kelly PA. Increased expression of prolactin receptor gene assessed by quantitative polymerase chain reaction in human breast tumors versus normal breast tissues. J Clin Endocrinol Metab 1998; 83:667-674
17. Bouchard B, Ormandy CJ, Di Santo JP, Kelly PA. Immune system development and function in prolactin receptor-deficient mice. J Immunol 1999; 163:576-582
18. Goffin V, Bernichtein S, Touraine P, Kelly PA. Development and potential clinical uses of human prolactin receptor antagonists. Endocr Rev 2005; 26:400-422
19. Bogorad RL, Courtillot C, Mestayer C, Bernichtein S, Harutyunyan L, Jomain JB, Bachelot A, Kuttenn F, Kelly PA, Goffin V, Touraine P. Identification of a gain-of-function mutation of the prolactin receptor in women with benign breast tumors. Proc Natl Acad Sci U S A 2008; 105:14533-14538
20. Rouet V, Bogorad RL, Kayser C, Kessal K, Genestie C, Bardier A, Grattan DR, Kelder B, Kopchick JJ, Kelly PA, Goffin V. Local prolactin is a target to prevent expansion of basal/stem cells in prostate tumors. Proc Natl Acad Sci U S A 2010; 107:15199-15204