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Molecular Medicine

Faculty

Helen P. Makarenkova, Ph.D.

Associate Professor of Molecular Medicine
Department of Molecular Medicine
California Campus
Laboratory Website
hmakarenk@scripps.edu
(858) 784-2621

Research Focus

Muscle development and regeneration

Skeletal muscle atrophy is a devastating disorder that occurs in a large number of chronic diseases such as cancer, diabetes, trauma, cystic fibrosis, HIV, aging and genetic disorders. Research in my laboratory focuses on the mechanisms of muscle regeneration and regulation of satellite cell (muscle progenitor cell) function.

Satellite cells are the resident stem cell of muscle: upon activation they give rise to a proliferating myoblast population that differentiates into myofibres. Recent progress in understanding the muscle regeneration process in complex degeneration models (rather than simple focal injury models) has suggested that disrupted signaling within the microenvironment is a driver of failed regeneration and fibrosis. Wnts play important roles in myogenic progression; however, excessive Wnt signaling is also associated with muscle pathology and muscle aging. Canonical Wnt signals are shown to induce differentiation of myoblasts in vitro and in vivo, although the precise mechanism of this remains unclear.

We have pioneered studies of homeobox factors Barx2 and Pax7 in Wnt-mediated myogenesis, as well as in negative-feedback to attenuate Wnt signalling. This study defines the mechanisms by which canonical Wnt induces myogenesis, the roles of Barx2 and Pax7 in mediating the effects of Wnt signals, and the roles of these factors in controlling Wnt feedback. Our research may help to identify drug or cell-based therapies to increase regeneration and reduce fibrosis.

Our goal is to develop the new strategies that can improve muscle repair.

Molecular mechanisms of lacrimal gland development and regeneration.

The dry eye condition involves chronic lack of ocular surface lubrication; symptoms include inflammation, pain, and in severe cases, blindness. In humans, the lacrimal gland (LG) is the primary contributor to the aqueous layer of the tear film, and dry eye syndrome is typically due to LG malfunction or damage.

Our goal is to develop new therapies able to restore lacrimal gland function. We believe that such therapies could be based on determining factors and mechanisms involved in the regulation of gland morphogenesis and regeneration or on isolation and transplanting stem or progenitor cells. Our ongoing work seeks to identify cell progenitors able to restore the function of the ‘diseased’ lacrimal gland as a critical first step in the development of stem cell-based strategies to treat patients with dry eye conditions. We have recently shown that members of the (FGF) family are important regulators of lacrimal gland homeostasis, regeneration and stem cell function. If we succeed, it would drastically improve the quality of life of people affected by dry eye.

 

Our long-term goal is to develop therapeutic approaches for the regeneration of damaged human lacrimal gland.

Professional Experience

2012-present :Assistant Professor, Department of Cell and molecular Biology, The Scripps Research Institute, La Jolla, CA The Scripps Research Institute, La Jolla, CA
2008-2012: Assistant Professor, Department of Neurobiology, The Scripps Research Institute, La Jolla, CA The Scripps Research Institute, La Jolla, CA
2001-2012:  Associate Fellow, The Neurosciences Institute, La Jolla, CA
1998-2001:  Associate Research Scientist, Skirball Institute Developmental Genetics Program, NYU Medical Center, New York, NY
1996-1997:  MRC Laboratory for Molecular and Cell Biology, University College, London
1994-1996: Wellcome Trust Fellow, Department of Anatomy and Developmental Biology, University College, London
1989-1994: Independent Research Scientist, Department of Physiology and Cell Structure, Institute of Cytology of Russian Academy of Sciences, St. Petersburg
1989: Ph.D. Zoology & Cell Biology, Leningrad State University

Awards & Professional Activities

1995-1997. The Wellcome Trust International Travelling Fellowship (grant No. 042268), Wellcome Trust

Selected References

For a complete list of publications: http://www.ncbi.nlm.nih.gov/myncbi/helen.makarenkova.1/bibliography/43825585/public/?sort=date&direction=ascending

Makarenkova H.P., Meech R. The Barx homeobox family in muscle development and regeneration. 2012. Int Rev Cell Mol Biol. 2012; 297:117-73

Voronov D, Gromova A, Liu D, Zoukhri D, Medvinsky A, Meech R, Makarenkova HP. Transcription factors Runx1 to 3 are expressed in the lacrimal gland epithelium and are involved in regulation of gland morphogenesis and regeneration. Invest Ophthalmol Vis Sci. 2013 May 1;54(5):3115-25. doi: 10.1167/iovs.13-11791. PubMed PMID: 23532528; PubMed Central PMCID: PMC3643397.

Meech R, Gonzalez KN, Barro M, Gromova A, Zhuang L, Hulin JA, Makarenkova HP. Barx2 is expressed in satellite cells and is required for normal muscle growth and regeneration. Stem Cells. 2012 Feb;30(2):253-65. doi: 10.1002/stem.777. PubMed PMID: 22076929; PubMed Central PMCID: PMC4547831.

Zhuang L, Hulin JA, Gromova A, Tran Nguyen TD, Yu RT, Liddle C, Downes M, Evans RM, Makarenkova HP, Meech R. Barx2 and Pax7 have antagonistic functions in regulation of wnt signaling and satellite cell differentiation. Stem Cells. 2014 Jun;32(6):1661-73. doi: 10.1002/stem.1674. PubMed PMID: 24753152; PubMed Central PMCID: PMC4134105.

Tsau C, Ito M, Gromova A, Hoffman MP, Meech R, Makarenkova HP. Barx2 and Fgf10 regulate ocular glands branching morphogenesis by controlling extracellular matrix remodeling. Development. 2011 Aug;138(15):3307-17. doi: 10.1242/dev.066241. PubMed PMID: 21750040; PubMed Central PMCID: PMC3133920.

Makarenkova HP, Hoffman MP, Beenken A, Eliseenkova AV, Meech R, Tsau C, Patel VN, Lang RA, Mohammadi M. Differential interactions of FGFs with heparan sulfate control gradient formation and branching morphogenesis. Sci Signal. 2009 Sep 15;2(88):ra55. doi: 10.1126/scisignal.2000304. PubMed PMID: 19755711; PubMed Central PMCID: PMC2884999.

Meech R, Gomez M, Woolley C, Barro M, Hulin JA, Walcott EC, Delgado J, Makarenkova HP. The homeobox transcription factor Barx2 regulates plasticity of young primary myofibers. PLoS One. 2010 Jul 15;5(7):e11612. doi: 10.1371/journal.pone.0011612. PubMed PMID: 20657655; PubMed Central PMCID: PMC2904708.

Makarenkova HP, Shestopalov VI. The role of pannexin hemichannels in inflammation and regeneration. Front Physiol. 2014 Feb 25;5:63. doi: 10.3389/fphys.2014.00063. eCollection 2014. Review. PubMed PMID: 24616702; PubMed Central PMCID: PMC3933922.

Umazume T, Thomas WM, Campbell S, Aluri H, Thotakura S, Zoukhri D, Makarenkova HP. Lacrimal Gland Inflammation Deregulates Extracellular Matrix Remodeling and Alters Molecular Signature of Epithelial Stem/Progenitor Cells. Invest Ophthalmol Vis Sci. 2015 Dec 1;56(13):8392-402. doi: 10.1167/iovs.15-17477. PubMed PMID: 26747770; PubMed Central PMCID: PMC4699416.

Aluri HS, Kublin CL, Thotakura S, Armaos H, Samizadeh M, Hawley D, Thomas WM, Leavis P, Makarenkova HP, Zoukhri D. Role of Matrix Metalloproteinases 2 and 9 in Lacrimal Gland Disease in Animal Models of Sjögren's Syndrome. Invest Ophthalmol Vis Sci. 2015 Aug;56(9):5218-28. doi: 10.1167/iovs.15-17003. PubMed PMID: 26244298; PubMed Central PMCID: PMC4530776.

Links

Fears for Tears

Molecular Medicine Seminar Series

CA Faculty

Asahara, Hiroshi
Balch, William E.
Boddy, Michael
Buxbaum, Joel
Catz, Sergio
Conti, Bruno
Cravatt, Benjamin
D'Lima, Darryl
DerMardirossian, Celine
Deryugina, Elena
Elias, Darlene
Encalada, Sandra
Felding, Brunhilde
Fowler, Velia
Friedlander, Martin
Gerace, Larry
Gottesfeld, Joel
Griffin, John
Hanneken, Anne
Heeb, Mary Jo
Henderson, Scott
Hoch, James
Joazeiro, Claudio
Johnson, Eric
Kanaji, Taisuke
Kay, Steve
Kelly, Jeffery
Koziol, James
Lamia, Katja
Lazzerini Denchi, Eros
Lipton, Stuart
Loring, Jeanne F.
Loskutoff, David
Lotz, Martin
Makarenkova, Helen P.
Mc Millan, Robert
Miles, Lindsey
Milner, Richard
Modena, Brian
Mosnier, Laurent
Paulson, James C.
Perego, Marta
Petrascheck, Michael
Pollard, Kenneth Michael
Quigley, James P.
Reed, Steven
Roberts, Edward
Rosen, Hugh
Ruggeri, Zaverio
Russell, Paul
Saez, Enrique
Smider, Vaughn
Srinivasan, Supriya
Steinhubl, Steven
Sutcliffe, J.
Tan, Eng
Topol, Eric
Vanderklish, Peter
Vogt, Peter K.
Waalen, Jill
Wiseman, Luke
Wittenberg, Curt
Wolan, Dennis W.
Wu, Peng
Wu, Xiaohua
Yang, Xiang-Lei
Yates III, John


FL Faculty

Bohn, Laura M.
Cameron, Michael
Duckett, Derek
Gill, Matt
Griffin, Patrick
Hansen, Scott
Kamenecka, Theodore
Kissil, Joseph
Luo, Junli
McDonald, Patricia
Miller, Courtney
Niedernhofer, Laura
Phinney, Donald G.
Robbins, Paul
Scampavia, Louis
Schimmel, Paul
Smith, Roy
Spicer, Timothy


Affiliated Faculty

Cline, Hollis
Kojetin, Douglas
Lairson, Luke
Paegel, Brian
Rumbaugh, Gavin
Shen, Ben
Solt, Laura A
Su, Andrew
Wu, Chunlei


Adjunct Faculty