Maksim Plikus, Ph.D.
University of California Irvine
Stem Cell Research Center
3018 Gross Hall, Irvine, CA 92697
Tel: (949) 824-1260
Associate Editor, Experimental Dermatology
Edward Mallinckrodt, Jr. Foundation grant, 2013
Dermatology Foundation research grant, 2013
Mechanisms of regeneration and stem cell control
Our laboratory studies how complex tissues and organs regenerate under normal conditions and in response to injury or disease. We aim to understand:
1. The nature of stem cell regulatory networks.
Homeostasis of many organs largely depends on the activities of tissue-specific stem cells. In the past, a lot of research has been focused on understanding how individual stem cells respond to signals from their micro-environment and decide between remaining quiescent and becoming activated. However, it was unclear if and how thousands of stem cells can coordinate their activities with one another.
Recently, we were able to study collective behavior of adult stem cells using the model of hair regeneration. Each hair has a prominent cluster of stem cells. Since there are thousands of hairs on the surface of the skin and skin is flat, together all hair stem cells form a two-dimensional network of clusters. Within this network each stem cell cluster listens to competing activating and inhibitory signals and decides between remaining quiescent and becoming activated based on the combined signaling message that it receives. Because the decision making rules are similar for every stem cell cluster, scaling of this behavior across the entire network results in striking patterns of hair regeneration.
To this end, we developed a mathematical approach that enables predictive modeling of the hair regeneration patterns. Using predictive power of the model, we showed how key BMP and WNT signaling pathways from the stem cell micro-environment become reused to mediate long-range communication between neighboring hair stem cell clusters. Currently we are interested in the following questions:
A) In addition to WNT and BMP, what other key signaling pathways are co-opted to regulate large-scale regeneration of hair stem cells? We are using the predictive computational modeling coupled with in vivo validation experiments to identify new players in the hair stem cell signaling network.
B) Does large-scale coordination exist among stem cells in tissues other than skin? We are looking to identify the analogous two- and three-dimensional stem cell networks in other organs.
C) Can stem cell coordination be modulated to design more physiologically-relevant stem cell-based therapies?
2. Stem cells behavior in response to organ injury.
Our laboratory is also interested to understand the natural limits of stem cell plasticity in response to injury. Our ongoing work shows that the regenerative abilities of adult mammalian skin are far greater than previously thought. In the center of large skin wounds cells can acquire an embryonic-like state and develop new, fully functioning hair follicles. We show that several days later large numbers of new adipocytes appear around neogenic hair follicles. These neogenic events can be so efficient that several months after wounding, scar tissue can hardly be distinguished from the normal skin. Adipose lineage was thought to never form de novo in adults. Our findings open up the exciting possibility that embryonic developmental programs can be entirely replicated in adults upon creating the proper signaling environment for the competent progenitor cells. Currently we are interested to understand:
A) What mechanism allows lineage-restricted adult cells to expand their developmental plasticity in response to wounding?
B) How can embryonic-like regeneration be enhanced to achieve scarless healing of adult tissues?
Selected Publications. See a complete list at http://www.ncbi.nlm.nih.gov/pubmed?term=plikus
- Yang J, Plikus MV, Komarova NL (2015). The role of symmetric stem cell divisions in tissue homeostasis. PLoS Comput Biol Journal.pcbi.1004629 Link
- Al Alam D, Agha EE, Sakurai R, Kheirollahi V, Moiseenko A, Danopoulos S, Shrestha A, Schmoldt C, Quantius J, Herold S, Chao CM, Tiozzo C, Langhe SD, Plikus MV, Thornton M, Grubbs B, Minoo P, Rehan V, Bellusci S (2015). Evidence for the involvement of Fibroblast Growth Factor 10 in lipofibroblast formation during embryonic lung development. Development Dev.109173 Link
- Oh JW, Kloepper J, Langan EA, Kim Y, Yeo J, Kim MJ, Hsi TC, Rose C, Yoon GS, Lee SJ, Seykora J, Kim JC, Sung YK, Kim M#, Paus R#, Plikus MV# (2015). A guide to studying human hair follicle cycling in vivo. J of Investigative Dermatology JID.2015.354 Link
- Beasley SM, Plikus MV, Spitale RC, Pedersen IM (2015). The emerging functions of regulatory RNA species in skin biology. Experimental Dermatology EXD.12850 Link
- Chen CC, Plikus MV, Tang PC, Widelitz RB, Chuong CM (2015). The modulatable stem cell niche: Tissue interactions during hair and feather follicle regeneration. Journal of Molecular Biology J.JMB.2015.07.009 Link
- Oh JW, Chung O, Cho YS, MacGregor GR, Plikus MV# (2015). Gene loss in keratinization programs accompanies adaptation of Cetacean skin to aquatic lifestyle. Experimental Dermatology 24: 572-573 Link
- Chen CC, Wang L, Plikus MV, Jiang TX, Murray PJ, Ramos R, Guerrero-Juarez CF, Hughes MW, Lee OK, Shi S, Widelitz RB, Lander AD, Chuong CM (2015). Organ-level quorum sensing directs regeneration in hair stem cell populations. Cell 161: 277–290 Link
- Wang X, Hsi TS, Guerrero-Juarez CF, Pham K, Cho K, McCusker CD, Monuki ES, Cho KWY, Gay DL, PlikusMV# (2015). Principles and mechanisms of regeneration in the mouse model for wound-induced hair follicle neogenesis. Regeneration REG2.38 Link
- Plikus MV, Van Spyk EN, Pham K, Geyfman M, Kumar V, Takahashi JS, Andersen B (2015). The circadian clock in skin: implications for adult stem cells, tissue regeneration, cancer, aging, and immunity. Journal of Biological Rhythms 30: 163-182 Link
- Oh JW, Lin SJ, Plikus MV# (2015). Regenerative metamorphosis in hairs and feathers: follicle as a programmable biological printer. Experimental Dermatology 24: 262-264 Link
- Zhang LJ, Guerrero-Juarez CF, Hata T, Bapat SP, Ramos R, Plikus MV, Gallo RL (2015). Dermal adipocytes protect against invasive Staphylococcus aureus skin infection. Science 347: 67-71 Link
UCI News: Skin fat is a newly recognized part of the body’s immune response
Orange County Register: Skin fat kills bacterial infections
- Geyfman M, Plikus MV, Treffeisen E, Andersen B, Paus R (2014). Resting no more: re-defining telogen, the maintenance stage of the hair growth cycle. Biological Reviews (Cambridge Philosophical Society) BRV.12151 Link
- Plikus MV#, Guerrero-Juarez CF, Treffeisen E, Gay DL# (2014). Epigenetic control of skin and hair regeneration after wounding. Experimental Dermatology 24: 167-170 Link
- Gay D, Yang CC, Plikus MV, Ito M, Rivera C, Treffeisen E, Doherty L, Spata M, Millar SE, Cotsarelis G (2014). CD133 expression correlates with membrane beta-catenin and e-cadherin loss from human hair follicle placodes during morphogenesis. J of Investigative Dermatology 135: 45-55 Link
- Guerrero-Juarez CF, Ramos R, Oh JW, Hsi TC, Plikus MV# (2014). Light-emitting hair follicles: studying skin regeneration with in vivo imaging. J of Investigative Dermatology 134: 1496-1498 Link
- Plikus MV#, Astrowski AA (2014). Deadly hairs, lethal feathers – convergent evolution of poisonous integument in mammals and birds. Experimental Dermatology 23: 466-468 Link
- Chen CC, Murray PJ, Jiang TX, Plikus MV, Chang YT, Lee OK, Widelitz RB, Chuong CM (2014). Regenerative hair waves in aging mice and extra-follicular modulators Follistatin, Dkk1 and Sfrp4. J of Investigative Dermatology 134: 2086-2096 Link
- Plikus MV# (2014). At the dawn of hair research – testing the limits of hair follicle regeneration. Experimental Dermatology 23: 314-315 Link
- Plikus MV, Chuong CM (2014). Macroenvironmental regulation of hair cycling and collective regenerative behavior. Cold Spring Harbor Perspectives in Medicine 4: a015198 Link
- Oh JW, Hsi TC, Guerrero-Juarez CF, Ramos R, Plikus MV# (2013). Organotypic skin culture. J of Investigative Dermatology 133: e14 Link
- Ramos R, Guerrero-Juarez CF, Plikus MV# (2013). Hair follicle signaling networks: a dermal papilla centric approach. J of Investigative Dermatology 133: 2306-2308 Link
- Plikus MV, Vollmers C, De la Cruz D, Chaix A, Ramos R, Panda S, Chuong CM (2013). Local circadian clock gates cell cycle progression of transient amplifying cells during regenerative hair cycling. PNAS 10: E2106–E2115 Link
Allure Magazine: Hair Fallout
Orange County Register: UCI In Focus: Researchers find timing is key for radiation treatment
- Gay D, Kwon O, Zhang Z, Spata M, Plikus MV, Holler PD, Ito M, Yang Z Treffeisen E, Kim CD, Nace A, Zhang X, Baratono S, Wang F, Ornitz DM, Millar SE, Cotsarelis G (2013). Fgf9 from dermal γδ T cells induces hair follicle neogenesis after wounding. Nature Medicine 19: 916-923 Link
2012 and earlier
- Plikus MV, Gay DL, Treffeisen E, Wang A, Supapannachart RJ, Cotsarelis G (2012). Epithelial stem cells and implications for wound repair. Seminars in Cell and Developmental Biology 23: 946-953 Link
- Plikus MV (2012). New activators and inhibitors in the hair cycle clock: targeting stem cells’ state of competence. J of Investigative Dermatology 132: 1321-1324 Link
- Plikus MV, Baker RE, Chen CC, Fare C, de la Cruz D, Andl T, Maini PK, Millar SE, Widelitz R, Chuong CM (2011). Self-organizing and stochastic behaviors during the regeneration of hair stem cells. Science 332: 586-589 Link
- Plikus MV, Widelitz RB, Maxson R, Chuong CM (2009). Analyses of regenerative wave patterns in adult hair follicle populations reveal macro-environmental regulation of stem cell activity. International J of Developmental Biology 53: 857-868 Link
- Plikus MV, Mayer JA, de la Cruz D, Baker RE, Maini PK, Maxson R, Chuong CM (2008). Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration. Nature 451: 340-344 Link
- Plikus MV and Chuong CM (2008). Complex hair cycle domain patterns and regenerative hair waves in living rodents. J of Investigative Dermatology 128: 1071-1080 Link
- Plikus MV#, Zhang Z, Chuong CM (2006). PubFocus: semantic MEDLINE/PubMed citations analytics through integration of controlled biomedical dictionaries and ranking algorithm. BMC Bioinformatics 7: 424 Link
- Plikus MV, Zeichner-David M, Mayer JA, Reyna J, Bringas P, Thewissen JG, Snead ML, Chai Y, Chuong CM (2005). Morphoregulation of teeth: modulating the number, size, shape and differentiation by tuning Bmp activity. Evolution and Development 7: 440-457 Link
- Plikus MV and Chuong CM (2004). Making waves with hairs. J of Investigative Dermatology 122: vii-ix Link
- Plikus MV, Wang WP, Liu J, Wang X, Jiang TX, Chuong CM (2004). Morpho-regulation of ectodermal organs: integument pathology and phenotypic variations in K14-Noggin engineered mice through modulation of bone morphogenic protein pathway. American J of Pathology 2004 164: 1099-1114 Link
- Gay D, Plikus MV, Treffeisen L, Wang A and Cotsarelis G (2013). Cutaneous Epithelial Stem Cells. In Principles of Tissue Engineering, 4th edition pp. 1581-1594. Elsevier Academic Press. Link
- Plikus MV, Sundberg, JP and Chuong, CM (2006). Mouse Skin Ectodermal Organs. In The Mouse in Biomedical Research pp. 692-730. Elsevier Academic Press. Link