Keep up with what's happening in the lab! Here we highlight any significant events that have been going on from conferences, to publications, to new staff!
CAMiLoD is opening the doors to the world with a grand opening full-day spectacle on July 4 in the Faculty of Dentistry. Great keynote speakers lead by Paul Kubes (University of Calgary), great talks, great food! Check here for program and registration.
April - June 2019
Just a small impression of the 2019 Gordon Conference on Tissue Repair and Regeneration organized by Will Wood and Kimberly Mace. Amazing meeting as always. Check the first row where Boris is securing Paul Kubes as our keynote speaker for the CAMiLoD Grand opening on July 4th.
The book “Dupuytren Disease and Hyperproliferative Disorders”, summarizing results of the international conference in Miami 2010 and featuring a chapter by Boris and Giulio Gabbiani. This book also appeared and was remarkably successful as an e-book with more than 45.000 chapter downloads since its publication! It is among the top 25% most downloaded books in its category. Looking forward to see you at our next conference in 2020 in Oxford, UK https://dupuytrensymposium.org/.
Well done honorary lab member Gertraud Eylert for successfully defending her Master thesis project: ‘Bio-Printing of Mesenchymal Stem Cells for Skin Reconstruction After Burns’.
Farwell to Trong Shen, as he embarks on a new career in the world of finance, we wish you much success and will miss your expertise. Many thanks Trong, for all your contributions to the lab. You left an imprint.
Welcome and congratulations to Melanie Kiebalo and Jennifer Guo for receiving CIHR IMHA funding to perform Undergraduate Research projects in our lab from May to August.
Congratulations to Pardis Pakshir. Her publication in Nature Communications was recommended by the Faculty of 1000 (F1000).
Congratulations to Monika Lodyga and Henna Karvonen for their co- publication in Science Signaling also being recommended by the F1000.
And congrats to alumni Marielle Walraven for her review article in Matrix Biology receiving another F1000 recommendation.
Congrats to Nina Noskovicova for being on a roll winning presentation prizes at the 25th Canadian Connective Tissue Conference for the best oral presentation, at the Gallie Day, Faculty of Medicine, University of Toronto for an e-poster presentation and at the Translational Research Workshop of the Department of Surgery, University of Toronto for an oral presentation selection.
CAMiLoD is opening the doors to the world with a grand opening full-day spectacle on July 4 in the Faculty of Dentistry. Great keynote speakers lead by Paul Kubes (University of Calgary), great talks, great food! Check here for program and registration.
January - March 2019
New Publication:Pakshir, P., Alizadehgiashi, M., Wong, B., Coelho, N.M., Chen, X., Gong, Z., Shenoy, V.B., McCulloch, C., and Hinz, B. (2019): Dynamic fibroblast contractions attract remote macrophages in fibrillar collagen matrix. Nature Communications
New Publication: Lodyga, M.*, Cambridge, E.* (*co-first author), Karvonen, H., Pakshir, P., Wu, B., Boo, S., Kiebalo, M., Kaarteenaho, R., Glogauer, M., Kapoor, M., Ask, K., and Hinz, B. (2019): Cadherin-11–mediated adhesion of macrophages to myofibroblasts establishes a profibrotic niche of active TGF-β. Science Signalling. Check the cover page and cover story by clicking here.
New Publication: Hinz, B., McCulloch, C.A., and Coelho, N.M. (2019): Mechanical regulation of myofibroblast phenoconversion and collagen contraction. Experimental Cell Research (e-pub ahead of print)
New Publication: Schleip, R., Gabbiani, G., Wilke, J., Naylor, I., Hinz B., Lehmann-Horn, F., Zorn, A, Jäger, H., Schreiner, S., and Klingler, W., (2019): Fascia is able to actively contract and thereby influence musculoskeletal dynamics: a histochemical and mechanographic investigation. Frontiers in Physiology - Clinical and Translational Physiology (e-pub ahead of print)
Welcome to Gilbert Pecoraro from the University of Reutlingen! Gilbert will perform a Bachelor project for a period of 5 months.
Boris finally found a solution to handle the traffic (see picture); get a number! Thanks, guys - best Christmas present ever!
Congratulations to Kyu Kim and Trong Shen for successfully defending their Master theses!
Congratulations to Pardis Pakshir and Ronen Schuster! The Hinz lab has been awarded with two post-doctoral fellowships through the Mitacs Accelerate program, amounting to a total of $165,000. Pardis will work on a 1-year project with Interface Biologics Inc., and Ronen who will be performing a 2-year project with Phenomic AI. See also the Dentistry Newsflash and click here.
We bid farewell to Mariëlle Walraven, who returning to the Netherlands in February, wishing her all the very best as she settles back, we will miss you greatly!
CAMiLoD is opening its doors to welcome microscopists from all over town. CAMiLoD are the Collaborative Advanced Microscopy Laboratories of Dentistry directed by Boris. CAMiLoD houses state-of-the-art imaging equipment, including high-speed high-resolution confocal microscopy, TIRF, life science atomic force microscopy, and more. Interested to use our services? Click here.
Congratulations to the first successful participants in the 1st AFM workshop organized by CAMiLoD. Enjoy poking cells and tissues at the nano-level.
Welcome to Joao Pedro Bronze de Firmino! Joao comes from the Ecole Polytechnique Fédérale de Lausanne and joins the Hinz lab as Post-Doc. Joao is imaging analysis specialist and will support the CAMiLoD endeavor!
October - December 2018
Farwell to Amanda Goodwin, we will miss Amanda’s helpful and positive nature - and scientific brilliance.
Welcome to Ronen Schuster joining us from Ben Gurion University of the Nagev, Israel. Wishing Ronen a productive Post Doc in our lab!
The impact of candy-wrapper: Our review “The ECM and TGF-β1: Tale of a strained relationship” (2015) is the top 3 downloaded and top 5 cited articles of ‘Matrix Biology’.
The relevance of fibrosis research: “The myofibroblast matrix: implications for tissue repair and fibrosis” (2012) is among the top 20 cited articles in the ‘Journal of Pathology’ and 2nd youngest article in that list. Among the top 10 cited articles, 4 are about fibrosis.
Congratulations to Pardis Pakshir on successfully defending her PhD thesis and for delivering her talk at the dentistry seminars.
And welcome Pardis Pakshir, new Post-Doc in the lab!
Congratulations Alumni Sandra Gribi! Published paper: Gribi S, du Bois de Dunilac S, Ghezzi D, Lacour SP. 2018. A micro-fabricated nerve-on-a-chip platform for rapid assessment of neural conduction in explanted peripheral nerve fibers. Nat Communications
Congratulations Alumni John Blaikley! Paper published: Cunningham PS, Maidstone R, Durrington HJ, et al., and Blaikley JF. 2018. Incidence of primary graft dysfunction after lung transplantation is altered by timing of allograft implantation. Thorax.
Just an impression of a session that Boris shared with Peter Friedl and Robert Schleip at the International Conference on Fascia Research in November in Berlin.
July - September 2018
New Publication: Walsh, S., Worrell, J., Fabre, A., Hinz, B., Kane, R., and Keane, M. (2018): Novel Differences in Gene Expression and Functional Capabilities of Myofibroblast Populations in Idiopathic Pulmonary Fibrosis. AJP Lung
New Publication:Warren, J., Im, M.*, Ballesteros, A., Ha, C., Moore, T., Lambert, F., Lucas, S., Hinz, B., Dveksler, G. (2018) Activation of latent transforming growth factor-?1, a conserved function for pregnancy-specific glycoproteins. Molecular Human Reproduction
Lab-trip: Thank-you everyone for another memorable Hinz Lab camping expedition; this time the Elora Gorge Conservation Area. We will never forget that it is 24 km from Kaufman’s Flats to Freeport Bridge, Kitchener when kayaking the Grand river.
Farewell to Melanie Kiebalo and Paul Wu who will return to their undergraduate student life after 4 months of joy and potential fame in the Hinz lab. Thanks a lot for your contributions to our research enterprise.
Welcome to Kristina Bei who will support Donna. Kristina took over from Nareg Kara-Yacoubian in September – Fare well Nareg!
A very warm farewell to Henna Karvonen after more than 2 years in the Hinz lab. Henna joined in April 2015 to study macrophages and myofibroblasts.Henna will return to Finland by the end of August. She will and continue the project on her fellowship for the Acadmy of Finland – while starting new endeavors. All the best!
Congratulations to Michele and Mariëlle Walraven and welcome to baby Luc! A temporary farewell to Mariëlle; looking forward to having you back early next year, relaxed after all that extra sleep.
April - June 2018
New publication:Asmani, M., Velumani, S., Li, Y., Wawrzyniak, N., Hsia, I., Chen, Z., Hinz, B., and Zhao, R. (2018): Fibrotic microtissue array to predict anti-fibrosis drug efficacy. Nature Communications
LTRR on the move: We said goodbye to good old Fitzgerald Building and moved to 124 Edward street into brand new research and office space. Thanks to the lab members for all your help and efforts before, during, and after the move. No major catastrophes happened, all our equipment seems to be functional and the lab is up and running again.
Cheers: Too bad that we could not move our paper celebration champagne bottles - not compatible with level 2 biosafety.
Congratulations to Marielle Walraven who was selected to present her work with a talk at the Meeting of the Skin Research Group, June 22-24, Montreal, QC, Canada.
Congratulations to Henna Karvonen and Monika Lodyga for winning the first Prize in the poster competition of the Canadian Connective Tissue Conference, Toronto, May 23-25, 2018 for their collaborative work.
Conference contributions: Members of LTRR contributed a total of 6 posters and 7 selected oral presentations to the following meetings:
Institute of Biomaterials and Biomedical Engineering Annual Research Conference, May 29, Toronto, ON, Canada
Canadian Connective Tissue Conference, May 23-25, Toronto, ON
Joint Meeting of the Wound Healing Society (WHS), European Tissue Repair Society (ETRS) and the Society for Advanced Wound Care (SAWC), April 25-29, Charlotte, NC, USA
Landscape of Translational Medicine Course, C-COMEND, EU training, Bayer, April 16-20, 2018, Berlin, Germany
Boris was ETRS program chair of the joint meeting of the Wound Healing Society (WHS), the European Tissue Repair Society (ETRS) and the Societies of Advanced Wound Care (SAWC) in Charlotte, NC, April 25-25, 2018.
The Symposium registered 120 attendees and featured a panel of world-leading experts, studying the mechanisms of fibrosis and tissue repair in different organs: Jeremy Duffield (lung and kidney), Neil Henderson (liver), Christina Philippeos (skin), Yuval Rinkevich (development), Fabio Rossi (Heart and skeletal muscle), and Robert Schwabe (liver and cancer stroma). Our keynote speaker, Giulio Gabbiani, founded this field of health research in the 1970’s by discovering activated fibroblasts –myofibroblasts– in skin wound tissue. Thankd to our session chairs Julie Fradette, Andras Kapus, and Michael Czubryt!
The symposium was organized with sponsor support from the University of Toronto and Toronto Health Initiatives: The Global Fibrosis Network, Medicine by Design, Bluerock Therapeutics, the Faculty of Dentistry, the Institute of Biomaterials and Biomedical Engineering, and the Canadian Connective Tissue Society, that held its annual meeting back-to-back. Thanks to all the supporters!!
Welcome to Deboki Naskar, who joined the lab as a post-doc, starting July 15, 2018. Deboki comes with a PhD from the Indian Institute of Technology Kharagpur, India in Biomaterials, Tissue Engineering, and Biomedical engineering. .
Welcome back Michelle Im! With a few more courses under her belt and a glowing GPA, Michelle will continue her project on cancer cell education.
Welcome Amanda Goodwin! Amanda comes from Gisli Jenkins’ Lab at the University of Nottingham to work on a lung fibrosis project from End-May to November. Smart move picking the Summer to visit.
Welcome and congratulations to Po-Han (Paul) Wu for receiving CIHR IMHA funding to perform a Summer Undergraduate Research Project in our lab (May-August).
Welcome to our summer volunteer Melanie Kiebalo who joins us from May-July. Melanie is a 2nd year undergrad student majoring in Human Biology and Psychology.
January - March 2018
New publication: Pakshir, P. and Hinz, B., (2018): The big five in fibrosis: macrophages, myofibroblasts, matrix, mechanics, and miscommunication. Matrix Biology
New publication: Walraven, M. and Hinz, B., (2018): New therapeutic approaches to control tissue repair and fibrosis: extracellular matrix as a game changer. Matrix Biology
New publication: Klingberg F, Chau G, Walraven M, Boo S, Koehler A, Chow ML, Olsen AL, Im M, Lodyga M, Wells RG, White ES, Hinz B. (2018) The ED-A domain enhances the capacity of fibronectin to store latent TGF-? binding protein-1 in the fibroblast matrix. Journal of Cell Science.
New publication: Sun, M., Ishii, R., Okumura, K., Krauszman, A., Breitling, S., Gomez, O., Hinek, A., Boo, S., Hinz, B., Connelly, K., Kuebler, W.M., Friedberg. M.K. (2018): Experimental right ventricular hypertension induces regional ?1 integrin mediated transduction of hypertrophic and pro-fibrotic right and left ventricular signaling. J American Heart Association (JAHA) (e-pub ahead of print)
Highlights: Our publication: “The ED-A domain enhances the capacity of FN to store LTBP-1 in the fibroblast matrix” has been selected for the ‘Research Highlights’ section of the Journal of Cell Science.
Cover Page: And one more: “The ED-A domain enhances the capacity of FN to store LTBP-1 in the fibroblast matrix” is featured with a cover page of the Journal of Cell Science, Volume 131
Fibrosis Research Rocks Dentistry: The Faculty of Dentistry was awarded ~$10 million in research funds from the CFI Innovation Fund and Ontario Research Fund. The award – largest in the Faculty’s history – will create Canada’s first comprehensive state-of-the-art research hub: “The Fibrosis Network” Please check out the Newsflash on the Faculty's web page here.
Pardis Pakshir (selected for talk), Marielle Walraven (selected for Poster Pitch), Henna Karvonen (Poster), and Boris (invited talk) presented work of the lab at the 8th Joint Meeting of the European Tissue Repair Society (ETRS) and the Wound Healing Society (WHS), April 25-29, 2018, Charlotte, NC, USA.
Trong Shen presented at the The Regenerative Medicine Symposium (April 25-26, 2018) in the Astellas Conference Room located in the Toronto General Hospital (585 University Avenue)
Congrats to Gyu-Tae (Kyu) Kim for winning the first prize for the best graduate student presentation at this year´s Faculty of Dentistry’s Research Day, February 13, 2018.
Hello and goodbye to Sindhu Kr (PhD student from the lab of Olivier Chassande, INSERM U 1026, BIOTIS, Université de Bordeaux). Sindhu stayed with us for the month of February to investigate fibrotic cell reactions on novel hydrogels. We hope you enjoyed Winter time in Toronto!
October - December 2017
New publication: Protic, O., Islam, MS., Greco, S., Giannubilo, SR., Lamanna, P., Petraglia, F., Ciavattini, A., Castellucci, M., Hinz, B., Ciarmela, P. (2017): Activin A in Inflammation, Tissue Repair, and Fibrosis: Possible Role as Inflammatory and Fibrotic Mediator of Uterine Fibroid Development and Growth. Seminars of Reproductive Medicine.
New publication: Rashedi, I., Talele, N., Wang, X.-H., Hinz, B., Radisic, M., and Keating, A. (2017): Collagen scaffold enhances the regenerative properties of mesenchymal stromal cells. PLoS One.
Welcome to Dong Ok Son (Donna), joining our lab as Research Associate. Donna comes from St. Michael’s hospital with a PhD in Applied Biochemistry (University of Tokio) and 10 years post-doctoral research experience. Excited to have you in the team!
Good-bye and Good-Luck to our extraordinary technician and master of all trades Stellar Boo. We wish Stellar much success in her new endeavors at Blue Rock Therapeutics! You will be dearly missed.
Good-bye and good luck for John Blaikley who left us by the end of December to continue his research with his own abandoned group in in Manchester – John, you have been an extraordinary enrichment of our team.
Welcome to Nina Noskovicova, who started a Post-Doc in the Hinz lab in November. Nina performed her PhD thesis in the group of Oliver Eickelberg (Munich, Germany) on projects related to TGF-? signaling in lung fibrosis and fibroblast biology.
January - March 2017
The Gordon Research Conference (GRC) and Seminar on Tissue Repair and Regeneration is around the corner: June 3-9, 2017. Please check the program here.
Also upcoming is the Toronto Fibrosis Workshop, taking place June 22-23, 2017 in Toronto, Princess Margaret Hospital, 610 University Ave., Room 7-605. Register here by May 31, 2017.
The 23rd Canadian Connective Tissue Society Conference will take place in Montreal, at the McGill New Residence Hall (NRH) from May 18-20, 2017. Abstract deadline: March 31 2017. Register here; submit abstract here.
The 4th Annual Skin Research Group Symposium will take place in Montreal, at the McGill New Residence Hall (NRH) from May 17-18, 2017. Abstract deadline: March 31 2017. Register here.
Welcome to Leonie Fecht and Nina Jetter! Both are here on an exchange program from the University of Reutlingen, Germany for 6 months of sheer joy and bliss – and to write a Bachelor thesis.
Congratulations to Boaz Wong and Akosua Vilaysane for being awarded with prestigious CIHR Undergraduate Research fellowships. Akosua achieved an impressive Rank 2 out of 80 applicants (2.5%). Job well done - we are looking forward to having you both in the lab for the Summer!
Farewell to Yousef Shafieyan who left by January 31 after 2.5 years of working with a lot of heart (cells) and rubber. His work will soon be submitted as two manuscripts. Yousef will be starting his own company.
Farewell to Tobias Kühl who left us by the end of February. Tobias will start a post-doc with Dr. David Lagares in the Massachusetts General Hospital, Boston after a brief stint back in his PhD lab in Freiburg. It was a privilege having you both in the lab. Best of luck with your future career!
New Publication: Niddam, A.F., Ebady, R., Bansal, A., Koehler, A., Hinz, B. and Moriarty, T.J. (2017): Plasma fibronectin stabilizes Borrelia burgdorferi-endothelial interactions under vascular shear stress by a catch bond mechanism. PNAS
New Publication: Coelho, N.M., Arora, P.D., van Putten, S.M., Boo, S., Petrovic, P., Hinz, B., and McCulloch, C.A. (2017): Discoidin Domain Receptor 1 Mediates Myosin Dependent Collagen Contraction. Cell Reports
October - December 2016
Check out this feature article on mechanical priming on the Faculty of Dentistry website: LINK.
Ho Ho Ho! We have had our annual LTRR Christmas lunch on December 12. The the annual Matrix Dynamics Group Christmas Party was celebrated on Friday, December 16, 2016. All Santas were secret.
Good bye and good luck to Markus Auler! All the very best in your upcoming adventures and hope you will stay in touch!
Welcome to Dr. Tobias Kuehl! Tobias comes from the Bruckner-Tuderman lab (University of Freiburg) and will join the LTRR until approximately March 2017 to work on part of his post-doc project. He will be utilizing soft silicone substrates to investigate dermal fibroblast from Dystrophic Epidermolysis Bullosa patients.
July - September 2016
LTRR is back on-line with an updated web presence. Many thanks to Alice Green and Boaz Wong for making this possible.
Welcometo Mariëlle Walraven who joined the lab as Post-Doc fellow on September 6, 2016. Mariëlle comes with a PhD in Genetics from the University of Amsterdam. Her thesis was on “Cellular and molecular mechanisms involved in scarless wound healing in the fetal skin”.
Welcome to Trong Shen who started on September 6, 2016. Trong comes with a Bachelor of Applied Science, Honours in Nanotechnology Engineering from the University of Waterloo and hopefully stays to start a Master thesis in January 2017.
LTRR on the water again: This year we spent three days on beautiful campsites at Mew Lake in Algonquin Park. We canoed for one day on the lakes with splendid weather conditions.
LTRR on the move: The University of Toronto has been successful in its bid to secure strategic research infrastructure funds from the Governments of Canada and Ontario, a portion of which has been earmarked for Dentistry. The Faculty of Dentistry is now embarking on project to renovate and revitalize its research infrastructure over the next two years. The Matrix Dynamics Group and LTRR will then leave Fitzgerald and join the Faculty physically. Check this related article from the Varsity Student Newspaper at U of T, featuring mind-boggling statements from Hinz.
New Publication: Langevin, H., Keely, P., Mao, J., Hodge, L., Schleip, R., Deng, G., Hinz, B., Swartz, M., de Valois, B., Zick, S., and Findley, T. (2016): Connecting (t)issues: How research in fascia biology can impact integrative oncology. Cancer Research
New Publication: Li, C.X., Talele, N.P., Boo, S., Knee-Walden, E., Koehler, A., Kapus, A., Speight, P., Balestrini, J.L., Hinz, B. (2016). Micro RNA miR-21 preserves the fibrotic mechanical memory of mesenchymal stem cells. Nature Materials
New Publication: Spinale, F.G., Frangogiannis, N.G., Hinz, B., Holmes, J.W., Kassiri, Z., Lindsey, M.L. (2016): Crossing Into the Next Frontier of Cardiac Extracellular Matrix Research. Circulation Research
New Publication: Hinz, B. (2016): The role of myofibroblasts in wound healing. Current Research in Translational Medicine
January - March 2016
Yousef Shafieyan was invited to present progress made on his Ted Rogers Centre for Heart Research (TRCHR) fellowship at the TRCHR 1st Scientific Symposium, May 12-13, 2016, Toronto.
Congratulations to Pardis Pakshir for passing her PhD qualifier!
Welcome to Michelle Im. Michelle will be starting on April 18 as Research Assistant in our lab to provide project support to our staff and students. Michelle comes with an MSc in Physiology and Pharmacology from the lab of Lina Dagnino at Western University.
Congratulations to Henna Karvonen for receiving a prestigious 3-year Postdoctoral Research Fellowship from the Research Council for Health of the Academy of Finland. The funding rate for this competition was only 11%, so very well done!!
New Publication: Bochaton, M.-L., Gabbiani, G., and Hinz, B. (2016) The Myofibroblast in Wound Healing and Fibrosis: Answered and Unanswered Questions. F1000 Biol Rep
New Publication: Dadson, K., Kovacevic, V., Rengasamy, P., Kim, G.H.E., Boo, S., Li, R.K., George, I., P. Schulze, C., Hinz, B., Sweeney, G. (2016), Cellular, structural and functional cardiac remodeling following pressure overload and unloading. International Journal of Cardiology
New Publication:Szeto, S.G., Narimatsu, M., Lu, M., Sidiqi, A., Chan, L., De Freitas, K.,Boo, S., Hinz, B., John, R., Wrana, J.L., Kapus, A., Yuen, D.A. (2016) YAP/TAZ are mechanoregulators of TGF-?-Smad signaling and renal fibrogenesis. J Am Soc Nephrol
New Publication:Varney, S.D, Betts, C.B., Zheng, R, Wu, L., Hinz, B., Zhou, J., Van De Water, L (2016) Hic-5 is required for myofibroblast differentiation by regulating mechanically dependent, MRTF-A nuclear accumulation J Cell Sci.
New Publication:Hinz, B. and Suki, B. Does breathing amplify fibrosis? An editorial on: Froese et al. (2016): Stretch Induced Activation of TGF-?1 in Pulmonary Fibrosis. American Journal of Respiratory AndCritical Care Medicine
April - June 2016
Congratulations to Pardis Pakshir and Ericka Knee-Walden for winning the Best Poster Presentation Prize in the PhD trainee category at the 22nd Canadian Connective Tissue Conference in Hamilton!
The lab attended collectively the 22nd Canadian Connective Tissue Conference at McMaster University in Hamilton June 1-3, 2016. Support the Canadian Connective Tissue Society.
Welcome to Markus Auler who will be performing a 6-month research project in the lab, officially starting on May 30, 2016. Markus will be working on the effect of specific micro RNAs on fibroblast contractility and differentiation phenotype.
Welcome to Boaz Wong who will be performing a summer research project in the lab starting on May 2, 2016. Boaz will support the macrophage crew. Also, congratulations to Boaz for obtaining an important Undergraduate Fellowship from CIHR.
Congratulations to Majd et al. (2015) for winning the prestigious Biomaterials 2015 Top Images poster award for an image published in the paper entitled “Novel micropatterns mechanically control fibrotic reactions at the surface of silicone implants”! The award was handed out (in absentia) at the World Biomaterials Congress in Montreal, Canada (May 21).
The Ted Rogers Centre for Heart Research (TRCHR) has selected the application “Multi-factorial Immune Cell Based Development of Non-Ischemic Cardiomyopathy” for a TRCHR Innovation Fund Seed Grant/New Ideas award. Principal Investigator is Dr. Slava Epelman, with Co-PIs Drs. Boris Hinz and Tania Watts.
New Publication:Nanchahal, J. and Hinz, B. (2016) Strategies to overcome the hurdles to treat fibrosis, a major unmet clinical need. PNAS