Tien Peng, MD

Associate Professor In Res
Pulmonary and Critical Care Division

Adult solid organs are composed of diverse cellular compartments with complex 3D organization that informs specific functions, with varying degrees of regenerative capacity in response to injury and tissue loss.  While resident tissue stem cells play an important role in the regenerative process, they are located within a cellular ecosystem (or “niche”) composed of various cell types that regulate stem cell function.  The Peng Lab is interested in how supportive niche cells modify the regenerative capacity of the stem cell, with the goal of deciphering cellular crosstalk that drives adaptive tissue regeneration. Our lab utilizes the lung as a model organ due to its immense cellular diversity and architectural complexity. 

Interested BMS/DSCB grad students are always welcome for lab rotations. Possible rotating projects include:

1. Establishment of organoid culture system to study tissue-tissue interaction. Our lab is interested in dissecting paracrine interactions that maintain normal tissue homeostasis, and modeling these behaviors in vitro. We have established organoid culture systems to study how various mesenchymal niches support epithelial survival and differentiation. The goal is to identify mesenchymal-derived factors that regulate epithelial progenitor behavior and vice versa.

2. Developing single-cell pipelines to dissect mesenchymal heterogeneity. We are focused on understanding how certain developmental pathways subdivide mesenchymal populations based on location and function. We are performing single-cell RNA sequencing using both the Drop-Seq and C1 Fluidigm platform to better understand how mesenchymal transcriptomes segregate based on location and cellular behavior.

3. Characterizing accelerated aging models. We have developed genetic tools to accelerate aging in the mesenchymal compartment in a temporal and spatially-selective manner. The goal is to identify tissue responses to the aging mesenchymal niche and evaluate factors that drive the aging phenotype.

Research Summary: 
Contribution of mesenchymal niche to homeostasis, repair, and aging

Websites

Publications: 

An in vivo screening platform identifies senolytic compounds that target p16INK4a+ fibroblasts in lung fibrosis.

The Journal of clinical investigation

Lee JY, Reyes NS, Ravishankar S, Zhou M, Krasilnikov M, Ringler C, Pohan G, Wilson C, Ang KK, Wolters PJ, Tsukui T, Sheppard D, Arkin MR, Peng T

In vivo protein turnover rates in varying oxygen tensions nominate MYBBP1A as a mediator of the hyperoxia response.

Science advances

Chen X, Haribowo AG, Baik AH, Fossati A, Stevenson E, Chen YR, Reyes NS, Peng T, Matthay MA, Traglia M, Pico AR, Jarosz DF, Buchwalter A, Ghaemmaghami S, Swaney DL, Jain IH

Bad Neighbors or Bad Neighborhoods: Pathogenic Residency of T Cells in COPD.

American journal of respiratory and critical care medicine

Peng T

Single-nuclei characterization of pervasive transcriptional signatures across organs in response to COVID-19.

eLife

COVID Tissue Atlas Consortium, Granados AA, Bucher S, Song H, Agrawal A, Chen AT, Peng T, Neff N, Pisco AO, Huang F, Wang B

Group 2 innate lymphoid cells constrain type 3/17 lymphocytes in shared stromal niches to restrict liver fibrosis.

bioRxiv : the preprint server for biology

Sbierski-Kind J, Cautivo KM, Wagner JC, Dahlgren MW, Nilsson J, Krasilnikov M, Mroz NM, Lizama CO, Gan AL, Matatia PR, Taruselli MT, Chang AA, Caryotakis S, O'Leary CE, Kotas M, Mattis AN, Peng T, Locksley RM, Molofsky AB

Dysregulated lung stroma drives emphysema exacerbation by potentiating resident lymphocytes to suppress an epithelial stem cell reservoir.

Immunity

Wang C, Hyams B, Allen NC, Cautivo K, Monahan K, Zhou M, Dahlgren MW, Lizama CO, Matthay M, Wolters P, Molofsky AB, Peng T

Sentinel p16INK4a+ cells in the basement membrane form a reparative niche in the lung.

Science (New York, N.Y.)

Reyes NS, Krasilnikov M, Allen NC, Lee JY, Hyams B, Zhou M, Ravishankar S, Cassandras M, Wang C, Khan I, Matatia P, Johmura Y, Molofsky A, Matthay M, Nakanishi M, Sheppard D, Campisi J, Peng T

Intersection of Inflammation and Senescence in the Aging Lung Stem Cell Niche.

Frontiers in cell and developmental biology

Allen NC, Reyes NS, Lee JY, Peng T

Human alveolar type 2 epithelium transdifferentiates into metaplastic KRT5+ basal cells.

Nature cell biology

Kathiriya JJ, Wang C, Zhou M, Brumwell A, Cassandras M, Le Saux CJ, Cohen M, Alysandratos KD, Wang B, Wolters P, Matthay M, Kotton DN, Chapman HA, Peng T

An inflammatory switch for stem cell plasticity.

Nature cell biology

Kathiriya JJ, Peng T

Gli1+ mesenchymal stromal cells form a pathological niche to promote airway progenitor metaplasia in the fibrotic lung.

Nature cell biology

Cassandras M, Wang C, Kathiriya J, Tsukui T, Matatia P, Matthay M, Wolters P, Molofsky A, Sheppard D, Chapman H, Peng T

The Role of Hedgehog Signaling in Adult Lung Regeneration and Maintenance.

Journal of developmental biology

Wang C, Cassandras M, Peng T

Adventitial Stromal Cells Define Group 2 Innate Lymphoid Cell Tissue Niches.

Immunity

Dahlgren MW, Jones SW, Cautivo KM, Dubinin A, Ortiz-Carpena JF, Farhat S, Yu KS, Lee K, Wang C, Molofsky AV, Tward AD, Krummel MF, Peng T, Molofsky AB

Endothelial toll-like receptor 4 maintains lung integrity via epigenetic suppression of p16INK4a.

Aging cell

Kim SJ, Shan P, Hwangbo C, Zhang Y, Min JN, Zhang X, Ardito T, Li A, Peng T, Sauler M, Lee PJ

Expansion of hedgehog disrupts mesenchymal identity and induces emphysema phenotype.

The Journal of clinical investigation

Wang C, Reyes de Mochel NS, Christenson SA, Cassandras M, Moon R, Brumwell AN, Byrnes LE, Li A, Yokosaki Y, Shan P, Sneddon JB, Jablons D, Lee PJ, Matthay MA, Chapman HA, Peng T

Emergence of a Wave of Wnt Signaling that Regulates Lung Alveologenesis by Controlling Epithelial Self-Renewal and Differentiation.

Cell reports

Frank DB, Peng T, Zepp JA, Snitow M, Vincent TL, Penkala IJ, Cui Z, Herriges MJ, Morley MP, Zhou S, Lu MM, Morrisey EE

Hedgehog actively maintains adult lung quiescence and regulates repair and regeneration.

Nature

Peng T, Frank DB, Kadzik RS, Morley MP, Rathi KS, Wang T, Zhou S, Cheng L, Lu MM, Morrisey EE

Long noncoding RNAs are spatially correlated with transcription factors and regulate lung development.

Genes & development

Herriges MJ, Swarr DT, Morley MP, Rathi KS, Peng T, Stewart KM, Morrisey EE

Distinct functions for Wnt/ß-catenin in hair follicle stem cell proliferation and survival and interfollicular epidermal homeostasis.

Cell stem cell

Choi YS, Zhang Y, Xu M, Yang Y, Ito M, Peng T, Cui Z, Nagy A, Hadjantonakis AK, Lang RA, Cotsarelis G, Andl T, Morrisey EE, Millar SE

Coordination of heart and lung co-development by a multipotent cardiopulmonary progenitor.

Nature

Peng T, Tian Y, Boogerd CJ, Lu MM, Kadzik RS, Stewart KM, Evans SM, Morrisey EE

Plasma levels of S100A4 in portopulmonary hypertension.

Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals

Peng T, Zamanian R, Krowka MJ, Benza RL, Roberts KE, Taichman DB, Rybak D, Trotter JF, Brown RS, Fallon MB, Kawut SM

Herpes simplex encephalitis in a patient with recurrent pituitary adenoma receiving radiation therapy.

American journal of clinical oncology

Peng T, Blakeley J, Cingolani E, Griffiths E, Grossman SA

The 1p-encoded protein stathmin and resistance of malignant gliomas to nitrosoureas.

Journal of the National Cancer Institute

Ngo TT, Peng T, Liang XJ, Akeju O, Pastorino S, Zhang W, Kotliarov Y, Zenklusen JC, Fine HA, Maric D, Wen PY, De Girolami U, Black PM, Wu WW, Shen RF, Jeffries NO, Kang DW, Park JK

Lentiviral vectors with two independent internal promoters transfer high-level expression of multiple transgenes to human hematopoietic stem-progenitor cells.

Molecular therapy : the journal of the American Society of Gene Therapy

Yu X, Zhan X, D'Costa J, Tanavde VM, Ye Z, Peng T, Malehorn MT, Yang X, Civin CI, Cheng L