Michaela Patterson, PhD
- Cell Biology, Neurobiology & Anatomy
PhD, University of California, Los Angeles, CA
BS, Bates College, Lewiston, ME
Cellular and molecular mechanisms that govern heart regeneration
Heart failure remains the leading cause of death worldwide necessitating continued efforts to identify therapeutic strategies that will stimulate tissue regeneration and functional recovery after an insult, such as a heart attack. My lab seeks to understand the genetic, molecular and cellular processes that allow for endogenous heart cells, cardiomyocytes, to re-enter the cell cycle and regenerate lost cardiac muscle tissue.
Recent discoveries: Our recent work published in Nature Genetics (Patterson et al., 2017) offered two important discoveries to the field of heart regeneration. First, it challenged the long-maintained notion that adult mammalian heart regeneration is insignificant and instead established that the capacity to regenerate one's heart after injury is a variable trait. In other words, there are some individuals capable of regenerating their hearts better than others. Supporting this, we took an unbiased, forward genetic approach to identify the gene(s) responsible for variable heart regeneration and validated the role of one of several candidate genes. Secondly, this work provided strength to the model that only a subset of cardiomyocytes, specifically the mononuclear diploid cardiomyocytes (MNDCMs), can contribute to myocardial regeneration. The lab intends to expand upon these findings in the following directions:
1) Exploiting natural variation to understand the genetic mechanisms of heart regeneration.
From our original genetic screen, several additional candidates remain unexplored for their roles in heart regeneration. Using complementary techniques, including viral delivery, drug-based manipulations, and genetic animal models, we will explore the function of these additional candidates both in heart development and regeneration. Future projects will also explore the epistatic relationship between the candidate genes.
2) Characterizing the nature of MNDCMs and assessing their role in heart regeneration.
To date, MNDCMs remain an understudied and underappreciated cell type within the heart. This project will make use of unpublished single cell RNAseq data to understand how they differ from the non-regeneration competent cells of the heart and to definitively test if they are the cell responsible for myocardial regeneration.
3) Of course, bring your own ideas!
We are actively recruiting trainees at all levels and welcome new ideas to transform the way we think about heart regeneration. If you are interested in joining or rotating in the Patterson Lab, please contact Michaela Patterson, PhD at email@example.com.
(Patterson M, Barske L, Van Handel B, Rau CD, Gan P, Sharma A, Parikh S, Denholtz M, Huang Y, Yamaguchi Y, Shen H, Allayee H, Crump JG, Force TI, Lien CL, Makita T, Lusis AJ, Kumar SR, Sucov HM.) Nat Genet. 2017 Sep;49(9):1346-1353.
(Yamaguchi Y, Cavallero S, Patterson M, Shen H, Xu J, Kumar SR, Sucov HM.) Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):2070-5.
(Patterson M, Gaeta X, Loo K, Edwards M, Smale S, Cinkornpumin J, Xie Y, Listgarten J, Azghadi S, Douglass SM, Pellegrini M, Lowry WE.) Stem Cell Reports. 2014 Nov 11;3(5):758-73.
(Palomares K, Vigant F, Van Handel B, Pernet O, Chikere K, Hong P, Sherman SP, Patterson M, An DS, Lowry WE, Mikkola HK, Morizono K, Pyle AD, Lee B.) J Virol. 2013 Feb;87(4):2094-108.
(Karumbayaram S, Lee P, Azghadi SF, Cooper AR, Patterson M, Kohn DB, Pyle A, Clark A, Byrne J, Zack JA, Plath K, Lowry WE.) Stem Cells Transl Med. 2012 Jan;1(1):36-43.
(Li JY, Patterson M, Mikkola HK, Lowry WE, Kurdistani SK.) PLoS Genet. 2012;8(8):e1002879.
(Patterson M, Chan DN, Ha I, Case D, Cui Y, Van Handel B, Mikkola HK, Lowry WE.) Cell Res. 2012 Jan;22(1):178-93.
(Zhang J, Tokatlian T, Zhong J, Ng QK, Patterson M, Lowry WE, Carmichael ST, Segura T.) Adv Mater. 2011 Nov 16;23(43):5098-103.
(Tchieu J, Kuoy E, Chin MH, Trinh H, Patterson M, Sherman SP, Aimiuwu O, Lindgren A, Hakimian S, Zack JA, Clark AT, Pyle AD, Lowry WE, Plath K.) Cell Stem Cell. 2010 Sep 03;7(3):329-42.
(Karumbayaram S, Novitch BG, Patterson M, Umbach JA, Richter L, Lindgren A, Conway AE, Clark AT, Goldman SA, Plath K, Wiedau-Pazos M, Kornblum HI, Lowry WE.) Stem Cells. 2009 Apr;27(4):806-11.
Patterson Lab members
Parker Foster, Research Associate
Mary Kolell, Research Technician
Xiangwen Peng, PhD, Postdoctoral Fellow
Alexandra Purdy, Research Technician
Samantha Swift, Graduate Student