Terence Partridge

Professor of Systematic Biology

United States of America

I obtained a B.Sc. in Zoology in 1962 and a Ph.D. on cell behaviour in 1970. After a year in the Musée Nationale D’Histoire Naturelle in Paris the working on rodent models of malaria and a year working as a Chemical Pathology Technician at St Mary’s Hospital, London, I took up an Assistant Lectureship  in the Department of Cell Biology in the University of Glasgow working on mechanisms of cell motility and adhesion[1]. On moving to the Department of Experimental Pathology in Charing Cross Hospital, I undertook much of the histopathological analysis of muscle biopsies and began research into myopathic disease, with special interest in Duchenne muscular dystrophy. This continued with my move to the MRC Clinical Sciences Centre in 1995, as head of the Muscle Cell Biology Group, and subsequently, on my statutory UK retirement in 2005, with a move to the Children’s National Medical Center in Washington DC with an interval in 2005-6  holding a Blaise Pascal Chair at the Genethon and Pasteur in Paris.

Over this time my research units in collaborations with others have introduced a number of fundamental advances in muscle research and introduced widely used new experimental tools.

1. Use of grafts of myogenic cells[2], portions of intact muscle[3], and of isolated muscle fibres[4,5] as research tools for investigation of muscle regeneration.
2. Development of methods for blocking background fluorescence from endogenous immunoglobulins when using mouse monoclonal antibodies, a variant of which is now marketed as ‘MOUSE ON MOUSE’[6].
3. In collaboration with Parmjt Jat and Mark Noble we developed the characterized conditionally immortal myogenic cells from the immortomouse. These have been widely used to generate reliable and reproducible myogenic clones from a number of mouse models of various myopathic and other diseases.
4. With Steve Wilton, we performed the first clear demonstrations of the potential efficacy of exon-skipping therapy for DMD and demonstrated the greater efficacy of Morpholino over 2`O-methyl chemistry in vivo for this type of intervention[7].
5. In my laboratory in Washington DC, we have followed this up by demonstrating the crucial interactive role of the inflammatory and regenerative mechanisms in delivery of morpholino antisense reagents into muscle fibres[8].
6. In collaboration with the immunologists in Washington and Binghamton, we have shown that an immune response can develop to dystrophin isoforms resulting from long-term application of exon-skipping in mice[9]
7. We have further investigated the influence of the inflammatory response on muscle regeneration in the DBA/2J-mdx mouse, where the fibro-adipocyte cell population appears to play a major role in subversion of satellite cell function[10].
8. More recently we have developed the use of xenografts of human muscle as experimental model systems that provide a further means of better approximating experimental systems to clinical translation analysis in man[11].

My experience across a broad spectrum of research methods, allied with my interest in development of stringent methods of data collection and analysis equips me well as a reviewer of much of the preclinical and clinical work that is presented to the TACT committee My current interests are in optimizing use of animal models of human myopathies with the aim of improving their predictive quality to facilitate a more efficient and effective  translation from preclinical research to clinical trials. More generally I am interested in developing robust quantitative analytical methods to properly characterize observations that reflect the biological mechanisms that underlie pathological processes.

1. Partridge T, Jones GE, Gillett R (1975) Cytochalasin B inhibits stabilisation of adhesions in fast-aggregating cell systems. Nature 253 (5493):632-634
2. Partridge TA, Morgan JE, Coulton GR, Hoffman EP, Kunkel LM (1989) Conversion of mdx myofibres from dystrophin-negative to -positive by injection of normal myoblasts. Nature 337 (6203):176-179. doi:10.1038/337176a0
3. Partridge TA, Grounds M, Sloper JC (1978) Evidence of fusion between host and donor myoblasts in skeletal muscle grafts. Nature 273 (5660):306-308
4. Collins CA, Olsen I, Zammit PS, Heslop L, Petrie A, Partridge TA, Morgan JE (2005) Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell 122 (2):289-301. doi:10.1016/j.cell.2005.05.010
5. Heslop L, Morgan JE, Partridge TA (2000) Evidence for a myogenic stem cell that is exhausted in dystrophic muscle. Journal of cell science 113 ( Pt 12):2299-2308
6. Lu QL, Partridge TA (1998) A new blocking method for application of murine monoclonal antibody to mouse tissue sections. J Histochem Cytochem 46 (8):977-984
7. Lu QL, Rabinowitz A, Chen YC, Yokota T, Yin H, Alter J, Jadoon A, Bou-Gharios G, Partridge T (2005) Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles. Proc Natl Acad Sci U S A 102 (1):198-203
8. Novak JS, Hogarth MW, Boehler JF, Nearing M, Vila MC, Heredia R, Fiorillo AA, Zhang A, Hathout Y, Hoffman EP, Jaiswal JK, Nagaraju K, Cirak S, Partridge TA (2017) Myoblasts and macrophages are required for therapeutic morpholino antisense oligonucleotide delivery to dystrophic muscle. Nat Commun 8 (1):941. doi:10.1038/s41467-017-00924-7
9. Vila MC, Novak JS, Benny Klimek M, Li N, Morales M, Fritz AG, Edwards K, Boehler JF, Hogarth MW, Kinder TB, Zhang A, Mazala D, Fiorillo AA, Douglas B, Chen YW, van den Anker J, Lu QL, Hathout Y, Hoffman EP, Partridge TA, Nagaraju K (2019) Morpholino-induced exon skipping stimulates cell-mediated and humoral responses to dystrophin in mdx mice. J Pathol 248 (3):339-351. doi:10.1002/path.5263
10. Mazala DA, Novak JS, Hogarth MW, Nearing M, Adusumalli P, Tully CB, Habib NF, Gordish-Dressman H, Chen YW, Jaiswal JK, Partridge TA (2020) TGF-beta-driven muscle degeneration and failed regeneration underlie disease onset in a DMD mouse model. JCI Insight 5 (6). doi:10.1172/jci.insight.135703
11. Zhang Y, King OD, Rahimov F, Jones TI, Ward CW, Kerr JP, Liu N, Emerson CP, Jr., Kunkel LM, Partridge TA, Wagner KR (2014) Human skeletal muscle xenograft as a new preclinical model for muscle disorders. Human molecular genetics 23 (12):3180-3188. doi:10.1093/hmg/ddu028

Disclosure statement:

Advisory committees:

• AFM Committee for evaluation of applications on fundamental myology
• Dutch Parent Project committee for evaluation of project applications
• Sarepta advisory group on duration of transgene expression in muscle
• Anagenesis advisory group on evaluation of promotion of myogenesis