Michael  Borchers

Michael T. Borchers , PhD

Professor

University of Cincinnati, Department of Internal Medicine, Medical Sciences Building
231 Albert Sabin Way, ML 0564
Cincinnati, Ohio 45267
Phone 513-558-4831
Fax 513-558-4858
Email michael.borchers@uc.edu

Education

Bachelor's Degree: University of Cincinnati Cincinnati, OH, 1993 (Biology)

Doctoral Degree: University of Cincinnati Cincinnati, OH, 1998 (Toxicology)

Postdoctoral Fellow: Mayo Clinic Scottsdale, AZ, 2002 (Immunology)

Research and Practice Interests

My research focuses on immune function in chronic pulmonary diseases.  Our laboratory examines local immune function in chronic obstructive pulmonary disease (COPD) patients and in mouse models of COPD. Specifically, we are interested in the role of natural killer cells, T cells, dendritic cells and macrophage in the response to viral and bacterial exacerbations in this disease.  In addition, we study immune function in two rare chronic lung diseases, Lymphangioleiomyomatosis (LAM), and pulmonary Langerhan’s cell histiocytosis (PLCH).  

Research Support

Grant: #R01 ES015036 Investigators:Borchers, Michael 09-01-2006 -08-31-2012 National Institute of Environmental Health Sciences Shared Mechanisms of Pulmonary Lymphocyte Activation by Bacteria and Toxicants Role:PI $2,106,143.00 Closed Level:Federal

Investigators:Borchers, Michael 11-15-2002 -11-14-2004 American Lung Association G Protein Signaling in Allergic Pulmonary Inflammation Role:PI $70,000.00 Closed Level:Private Non-Profit

Investigators:Borchers, Michael 11-01-2003 -10-31-2006 Health Effects Institute T-Cell Sub-Populations Regulate Airway Inflammation and Injury Following Acrolein Exposures Role:PI $299,867.00 Closed Level:Private Non-Profit

Grant: #U01 ES015675 / 0006165 Investigators:Borchers, Michael; Medvedovic, Mario; Tichelaar, Jay 07-01-2007 -05-31-2011 National Institute of Environmental Health Sciences Functional Genomics of Chemical-Induced Acute Lung Injury Role:PI $111,619.00 Closed Level:Federal

Grant: #113714-1 / R01 HL 085655 Investigators:Borchers, Michael 04-01-2008 -03-31-2010 National Heart, Lung and Blood Institute Role of Metalloproteinases in Mucin Overproduction in COPD Role:PI $78,000.00 Closed Level:Federal

Grant: #SRS 006140 Investigators:Borchers, Michael 07-01-2009 -06-30-2012 Flight Attendant Medical Research Institute Origin and Function of CD8 T Cell Expansions Following Long-Term Cigarette Smoke Exposure Role:PI $319,702.00 Closed Level:Private Non-Profit

Grant: #R21 ES017316 Investigators:Adhikari, Atin; Borchers, Michael; Grinshpun, Sergey; Reponen, Tiina 09-20-2010 -08-31-2013 National Institute of Environmental Health Sciences TLR Ligand and Pesticide Exposures in Farms: Role in Atopic Immune Responses Role:Collaborator $429,395.00 Active Level:Federal

Grant: #R21 HL109635 Investigators:Borchers, Michael; Greis, Kenneth 08-15-2011 -07-31-2013 National Heart, Lung and Blood Institute Novel Reagents in Mouse Models of Autoimmune COPD Role:PI $431,750.00 Active Level:Federal

Grant: #FAMRI Grant Investigators:Borchers, Michael 07-01-2012 -06-30-2015 Flight Attendant Medical Research Institute Regulation of CS-Induced Pathogenic T cells Role:PI $325,500.00 Active Level:Private Non-Profit

Grant: #R01 HL119538 Investigators:Borchers, Michael; Greis, Kenneth 04-01-2014 -03-31-2018 National Heart, Lung and Blood Institute Clec5a regulation of Macrophage function in COPD Role:PI $396,250.00 Awarded Level:Federal

Grant: #60040118 / R01 HL118268 Investigators:Borchers, Michael 01-01-2014 -12-31-2016 National Heart, Lung and Blood Institute Role of ZIP8 in first hand cigarette smoke exposure-mediated lung injury Role:PI $37,314.00 Awarded Level:Federal

Grant: #LAM0117P01-16 Investigators:Borchers, Michael 01-15-2016 -01-14-2017 Lymphangioleiomyomatosis Foundation (LAM) NKG2D Receptor-Ligand Interactions in LAM Pathogenesis Role:PI $25,000.00 Active Level:Private Non-Profit

Grant: #R01 HL135122 Investigators:Borchers, Michael; McCormack, Francis; Yu, Jane 12-07-2017 -11-30-2021 National Heart, Lung and Blood Institute Pulmonary Epithelial Dynamics and Innate Host Defense Role:Collaborator $506,717.00 Active Level:Federal

Grant: #LAM0126E01-18 Investigators:Borchers, Michael 01-14-2018 -01-15-2020 Lymphangioleiomyomatosis Foundation (LAM) Natural Killer Cell Phenotype and Function in Lymphangioleiomyomatosis Role:PI $150,000.00 Active Level:Private Non-Profit

Grant: #R01HL141236 Investigators:Borchers, Michael; Greis, Kenneth 01-01-2019 -12-31-2022 National Heart, Lung and Blood Institute Natural Killer Cell Functions in Lymphangioleiomyomatosis Role:PI $388,340.00 Awarded Level:Federal

Grant: #RSG-19-111-01-CCE Investigators:Borchers, Michael; Hinrichs, Benjamin; Wise-Draper, Trisha; Zender, Chad 01-01-2020 -12-31-2023 American Cancer Society - National Chapter Harnessing the Natural Killer Cytotoxic Response in Head and Neck Cancer Role:Collaborator $792,000.00 Active Level:Private Non-Profit

Grant: #CCHMC 312341 / R01HL149631 Investigators:Borchers, Michael 06-01-2020 -05-31-2024 National Heart, Lung and Blood Institute Molecular Mechanisms Regulated by FOXM1 in Chronic Lung Remodeling Role:PI $36,984.00 Active Level:Federal

Grant: #R01HL162662 Investigators:Borchers, Michael; McCormack, Francis 05-01-2023 -04-30-2027 National Heart, Lung and Blood Institute Molecular and Cellular Pathogenesis of Pulmonary Langerhans Cell Histiocytosis Role:PI 567803.00 Awarded Level:Federal

Grant: #R01HL168588 Investigators:Borchers, Michael; Kotagiri, Nalinikanth; McCormack, Francis; Weiss, Alison; Xie, Changchun 07-01-2023 -06-30-2028 National Heart, Lung and Blood Institute Siderophore based molecular imaging of pulmonary infections Role:Collaborator 678865.00 Awarded Level:Federal

Grant: #UZ 735290; 7R01HL149631-04 Investigators:Borchers, Michael -05-31-2024 National Heart, Lung and Blood Institute Molecular Mechanisms Regulated by FOXM1 in Chronic Lung Remodeling Role:PI 0.00 Hold Level:Federal

Publications

Peer Reviewed Publications

Hassett, Daniel J; Borchers, Michael T; Panos, Ralph J (2014. ) Chronic obstructive pulmonary disease (COPD): evaluation from clinical, immunological and bacterial pathogenesis perspectives.Journal of microbiology (Seoul, Korea), , 52 (3 ) ,211-26 More Information

Borchers, Michael T; Kratzer, Adelheid; Taraseviciene-Stewart, Laimute (2014. ) Second hand smoke and COPD: lessons from animal studies.Frontiers in physiology, , 5 ,144 More Information

Eppert, Bryan L; Wortham, Brian W; Flury, Jennifer L; Borchers, Michael T (2013. ) Functional characterization of T cell populations in a mouse model of chronic obstructive pulmonary disease.Journal of immunology (Baltimore, Md. : 1950), , 190 (3 ) ,1331-40 More Information

Wortham, Brian W; Eppert, Bryan L; Flury, Jennifer L; Morgado Garcia, Sara; Borchers, Michael T (2013. ) TLR and NKG2D signaling pathways mediate CS-induced pulmonary pathologies.PloS one, , 8 (10 ) ,e78735 More Information

Wortham, Brian W; Eppert, Bryan L; Motz, Greg T; Flury, Jennifer L; Orozco-Levi, Mauricio; Hoebe, Kasper; Panos, Ralph J; Maxfield, Melissa; Glasser, Stephan W; Senft, Albert P; Raulet, David H; Borchers, Michael T (2012. ) NKG2D mediates NK cell hyperresponsiveness and influenza-induced pathologies in a mouse model of chronic obstructive pulmonary disease.Journal of immunology (Baltimore, Md. : 1950), , 188 (9 ) ,4468-75 More Information

Motz, Gregory T; Eppert, Bryan L; Wesselkamper, Scott C; Flury, Jennifer L; Borchers, Michael T (2010. ) Chronic cigarette smoke exposure generates pathogenic T cells capable of driving COPD-like disease in Rag2-/- mice.American journal of respiratory and critical care medicine, , 181 (11 ) ,1223-33 More Information

Eppert, Bryan L; Motz, Gregory T; Wortham, Brian W; Flury, Jennifer L; Borchers, Michael T (2010. ) CCR7 deficiency leads to leukocyte activation and increased clearance in response to pulmonary Pseudomonas aeruginosa infection.Infection and immunity, , 78 (5 ) ,2099-107 More Information

Motz, Gregory T; Eppert, Bryan L; Wortham, Brian W; Amos-Kroohs, Robyn M; Flury, Jennifer L; Wesselkamper, Scott C; Borchers, Michael T (2010. ) Chronic cigarette smoke exposure primes NK cell activation in a mouse model of chronic obstructive pulmonary disease.Journal of immunology (Baltimore, Md. : 1950), , 184 (8 ) ,4460-9 More Information

Caldwell, Charles C; Chen, Yi; Goetzmann, Holly S; Hao, Yonghua; Borchers, Michael T; Hassett, Daniel J; Young, Lisa R; Mavrodi, Dmitri; Thomashow, Linda; Lau, Gee W (2009. ) Pseudomonas aeruginosa exotoxin pyocyanin causes cystic fibrosis airway pathogenesis.The American journal of pathology, , 175 (6 ) ,2473-88 More Information

Borchers, Michael T; Wesselkamper, Scott C; Deshmukh, Hitesh; Beckman, Erin; Medvedovic, Mario; Sartor, Maureen; Leikauf, George D (2009. ) The role of T cells in the regulation of acrolein-induced pulmonary inflammation and epithelial-cell pathology. Research report (Health Effects Institute), , (146 ) ,5-29

Deshmukh, Hitesh S; McLachlan, Anne; Atkinson, Jeffrey J; Hardie, William D; Korfhagen, Thomas R; Dietsch, Maggie; Liu, Yang; Di, Peter Y P; Wesselkamper, Scott C; Borchers, Michael T; Leikauf, George D (2009. ) Matrix metalloproteinase-14 mediates a phenotypic shift in the airways to increase mucin production.American journal of respiratory and critical care medicine, , 180 (9 ) ,834-45 More Information

Borchers, Michael T; Wesselkamper, Scott C; Curull, Victor; Ramirez-Sarmiento, Alba; Sánchez-Font, Albert; Garcia-Aymerich, Judith; Coronell, Carlos; Lloreta, Josep; Agusti, Alvar G; Gea, Joaquim; Howington, John A; Reed, Michael F; Starnes, Sandra L; Harris, Nathaniel L; Vitucci, Mark; Eppert, Bryan L; Motz, Gregory T; Fogel, Kevin; McGraw, Dennis W; Tichelaar, Jay W; Orozco-Levi, Mauricio (2009. ) Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease.The Journal of clinical investigation, , 119 (3 ) ,636-49 More Information

Motz, Gregory T; Eppert, Bryan L; Sun, Guangyun; Wesselkamper, Scott C; Linke, Michael J; Deka, Ranjan; Borchers, Michael T (2008. ) Persistence of lung CD8 T cell oligoclonal expansions upon smoking cessation in a mouse model of cigarette smoke-induced emphysema. Journal of immunology (Baltimore, Md. : 1950), , 181 (11 ) ,8036-43

Wesselkamper, Scott C; Eppert, Bryan L; Motz, Gregory T; Lau, Gee W; Hassett, Daniel J; Borchers, Michael T (2008. ) NKG2D is critical for NK cell activation in host defense against Pseudomonas aeruginosa respiratory infection. Journal of immunology (Baltimore, Md. : 1950), , 181 (8 ) ,5481-9

Borchers, Michael T; Wesselkamper, Scott C; Eppert, Bryan L; Motz, Gregory T; Sartor, Maureen A; Tomlinson, Craig R; Medvedovic, Mario; Tichelaar, Jay W (2008. ) Nonredundant functions of alphabeta and gammadelta T cells in acrolein-induced pulmonary pathology.Toxicological sciences : an official journal of the Society of Toxicology, , 105 (1 ) ,188-99 More Information

Deshmukh, Hitesh S; Shaver, Colleen; Case, Lisa M; Dietsch, Maggie; Wesselkamper, Scott C; Hardie, William D; Korfhagen, Thomas R; Corradi, Massimo; Nadel, Jay A; Borchers, Michael T; Leikauf, George D (2008. ) Acrolein-activated matrix metalloproteinase 9 contributes to persistent mucin production.American journal of respiratory cell and molecular biology, , 38 (4 ) ,446-54 More Information

Borchers, Michael T; Wesselkamper, Scott C; Harris, Nathaniel L; Deshmukh, Hitesh; Beckman, Erin; Vitucci, Mark; Tichelaar, Jay W; Leikauf, George D (2007. ) CD8+ T cells contribute to macrophage accumulation and airspace enlargement following repeated irritant exposure.Experimental and molecular pathology, , 83 (3 ) ,301-10 More Information

McLachlan, Anne; Borchers, Michael; Velayutham, Prakash; Wagner, Michael; Limbach, Patrick A (2006. ) Characterizing the reproducibility of a protein profiling method for the analysis of mouse bronchoalveolar lavage fluid.Journal of proteome research, , 5 (11 ) ,3059-65 More Information

Borchers, Michael T; Harris, Nathaniel L; Wesselkamper, Scott C; Vitucci, Mark; Cosman, David (2006. ) NKG2D ligands are expressed on stressed human airway epithelial cells.American journal of physiology. Lung cellular and molecular physiology, , 291 (2 ) ,L222-31 More Information

Borchers, Michael T; Harris, Nathaniel L; Wesselkamper, Scott C; Zhang, Shiping; Chen, Yi; Young, Lisa; Lau, Gee W (2006. ) The NKG2D-activating receptor mediates pulmonary clearance of Pseudomonas aeruginosa.Infection and immunity, , 74 (5 ) ,2578-86 More Information

Young, Lisa R; Borchers, Michael T; Allen, Holly L; Gibbons, Reta S; McCormack, Francis X (2006. ) Lung-restricted macrophage activation in the pearl mouse model of Hermansky-Pudlak syndrome. Journal of immunology (Baltimore, Md. : 1950), , 176 (7 ) ,4361-8

Wesselkamper, Scott C; McDowell, Susan A; Medvedovic, Mario; Dalton, Timothy P; Deshmukh, Hitesh S; Sartor, Maureen A; Case, Lisa M; Henning, Lisa N; Borchers, Michael T; Tomlinson, Craig R; Prows, Daniel R; Leikauf, George D (2006. ) The role of metallothionein in the pathogenesis of acute lung injury.American journal of respiratory cell and molecular biology, , 34 (1 ) ,73-82 More Information

Wesselkamper, Scott C; Case, Lisa M; Henning, Lisa N; Borchers, Michael T; Tichelaar, Jay W; Mason, John M; Dragin, Nadine; Medvedovic, Mario; Sartor, Maureen A; Tomlinson, Craig R; Leikauf, George D (2005. ) Gene expression changes during the development of acute lung injury: role of transforming growth factor beta.American journal of respiratory and critical care medicine, , 172 (11 ) ,1399-411 More Information

Deshmukh, Hitesh S; Case, Lisa M; Wesselkamper, Scott C; Borchers, Michael T; Martin, Linda D; Shertzer, Howard G; Nadel, Jay A; Leikauf, George D (2005. ) Metalloproteinases mediate mucin 5AC expression by epidermal growth factor receptor activation.American journal of respiratory and critical care medicine, , 171 (4 ) ,305-14 More Information

Leikauf, George D; Borchers, Michael T; Prows, Daniel R; Simpson, Leigh G (2002. ) Mucin apoprotein expression in COPD. Chest, , 121 (5 Suppl ) ,166S-182S

Borchers, M T; Wesselkamper, S; Wert, S E; Shapiro, S D; Leikauf, G D (1999. ) Monocyte inflammation augments acrolein-induced Muc5ac expression in mouse lung. The American journal of physiology, , 277 (3 Pt 1 ) ,L489-97

Borchers, M T; Carty, M P; Leikauf, G D (1999. ) Regulation of human airway mucins by acrolein and inflammatory mediators. The American journal of physiology, , 276 (4 Pt 1 ) ,L549-55

Borchers, M T; Wert, S E; Leikauf, G D (1998. ) Acrolein-induced MUC5ac expression in rat airways. The American journal of physiology, , 274 (4 Pt 1 ) ,L573-81

Balasubramaniam, A; Ujhelyi, M; Borchers, M; Huang, Y; Zhai, W; Zhou, Y; Johnson, M; Sheriff, S; Fischer, J E (1996. ) Antagonistic properties of centrally truncated analogs of [D-Trp(32)]NPY.Journal of medicinal chemistry, , 39 (5 ) ,1142-7 More Information

Chance, W T; Balasubramaniam, A; Borchers, M; Fischer, J E (1995. ) Refractory hypothalamic adenylate cyclase in anorectic tumor-bearing rats: implications for NPY-induced feeding. Brain research, , 691 (1-2 ) ,180-4

Norman, A B; Borchers, M T; Wachendorf, T J; Price, A L; Sanberg, P R (1989. ) Loss of D1 and D2 dopamine receptors and muscarinic cholinergic receptors in rat brain following in vitro polytron homogenization. Brain research bulletin, , 22 (4 ) ,633-6

Liu, Huan; Jakubzick, Claudia; Osterburg, Andrew R; Nelson, Rebecca L; Gupta, Nishant; McCormack, Francis X; Borchers, Michael T (2017. ) Dendritic Cell Trafficking and Function in Rare Lung Diseases.American journal of respiratory cell and molecular biology, , More Information

Osterburg, Andrew R; Nelson, Rebecca L; Yaniv, Benyamin Z; Foot, Rachel; Donica, Walter R F; Nashu, Madison A; Liu, Huan; Wikenheiser-Brokamp, Kathryn A; Moss, Joel; Gupta, Nishant; McCormack, Francis X; Borchers, Michael T (2016. ) NK cell activating receptor ligand expression in lymphangioleiomyomatosis is associated with lung function decline.JCI insight, , 1 (16 ) ,e87270 More Information

Wortham, Brian W; Eppert, Bryan L; Flury, Jennifer L; Garcia, Sara Morgado; Donica, Walter R; Osterburg, Andrew; Joyce-Shaikh, Barbara; Cua, Daniel J; Borchers, Michael T (2016. ) Cutting Edge: CLEC5A Mediates Macrophage Function and Chronic Obstructive Pulmonary Disease Pathologies.Journal of immunology (Baltimore, Md. : 1950), , 196 (8 ) ,3227-31 More Information

Li, Chenggang; Liu, Xiaolei; Liu, Yang; Zhang, Erik; Medepalli, Kantha; Masuda, Kouhei; Li, Na; Wikenheiser-Brokamp, Kathryn A; Osterburg, Andrew; Borchers, Michael T; Kopras, Elizabeth J; Plas, David R; Sun, Julia; Franz, David N; Capal, Jamie K; Mays, Maxwell; Sun, Yang; Kwiatkowski, David J; Alayev, Anya; Holz, Marina K; Krueger, Darcy A; Siroky, Brian J; Yu, Jane J (2017. ) Tuberin Regulates Prostaglandin Receptor-Mediated Viability, via Rheb, in mTORC1-Hyperactive Cells.Molecular cancer research : MCR, , 15 (10 ) ,1318-1330 More Information

Liu, Huan; Osterburg, Andrew R; Flury, Jennifer; Huang, Shuo; McCormack, Francis X; Cormier, Stephania A; Borchers, Michael T (2018. ) NKG2D is Required for Regulation of Lung Pathology and Dendritic Cell Function Following RSV Infection.The Journal of infectious diseases, , More Information

Osterburg, Andrew R; Lach, Laura; Panos, Ralph J; Borchers, Michael T (2018. ) Peripheral Blood Natural Killer Cell Phenotypes Associated with Exacerbation Risk in Patients with Chronic Obstructive Pulmonary Disease.Annals of the American Thoracic Society, , 15 (Supplement_4 ) ,S288-S289 More Information

Knoell, Daren L; Smith, Deandra; Bao, Shengying; Sapkota, Muna; Wyatt, Todd A; Zweier, Jay L; Flury, Jennifer; Borchers, Michael T; Knutson, Mitch (2020. ) Imbalance in zinc homeostasis enhances lung Tissue Loss following cigarette smoke exposure.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), , 60 ,126483 More Information

Choi, Woosuk; Choe, Shawn; Lin, Jingjun; Borchers, Michael T; Kosmider, Beata; Vassallo, Robert; Limper, Andrew H; Lau, Gee W (2020. ) Exendin-4 restores airway mucus homeostasis through the GLP1R-PKA-PPAR?-FOXA2-phosphatase signaling.Mucosal immunology, , 13 (4 ) ,637-651 More Information

Rajaram, Sanjeeth; Canaday, Laura M; Ochayon, David E; Rangel, Kelly M; Ali, Ayad; Gyurova, Ivayla E; Krishnamurthy, Durga; Fletcher, Jonathan S; Reighard, Seth D; Cox, Andrew; Weirauch, Matthew T; Kottyan, Leah C; Deshmukh, Hitesh; Zacharias, William J; Borchers, Michael T; Waggoner, Stephen N (2020. ) The Promise and Peril of Natural Killer Cell Therapies in Pulmonary Infection.Immunity, , 52 (6 ) ,887-889 More Information

Ochayon, David E; Ali, Ayad; Alarcon, Pablo C; Krishnamurthy, Durga; Kottyan, Leah C; Borchers, Michael T; Waggoner, Stephen N (2020. ) IL-33 promotes type 1 cytokine expression via p38 MAPK in human NK cells.Journal of leukocyte biology, , 107 (4 ) ,663-671 More Information

Shaw, Brian; Borchers, Michael; Zander, Dani; Gupta, Nishant (2020. ) Pulmonary Langerhans Cell Histiocytosis.Seminars in respiratory and critical care medicine, , 41 (2 ) ,269-279 More Information

Liu, Huan; Osterburg, Andrew R; Flury, Jennifer; Swank, Zulma; McGraw, Dennis W; Gupta, Nishant; Wikenheiser-Brokamp, Kathryn A; Kumar, Ashish; Tazi, Abdellatif; Inoue, Yoshikazu; Hirose, Masaki; McCormack, Francis X; Borchers, Michael T (2020. ) MAPK mutations and cigarette smoke promote the pathogenesis of pulmonary Langerhans cell histiocytosis.JCI insight, , 5 (4 ) , More Information

Osterburg, Andrew R; Lach, Laura; Panos, Ralph J; Borchers, Michael T (2020. ) Unique natural killer cell subpopulations are associated with exacerbation risk in chronic obstructive pulmonary disease.Scientific reports, , 10 (1 ) ,1238 More Information

Suzuki, Takuji; McCarthy, Cormac; Carey, Brenna C; Borchers, Michael; Beck, David; Wikenheiser-Brokamp, Kathryn A; Black, Dianna; Chalk, Claudia; Trapnell, Bruce C (2020. ) Increased Pulmonary GM-CSF Causes Alveolar Macrophage Accumulation. Mechanistic Implications for Desquamative Interstitial Pneumonitis.American journal of respiratory cell and molecular biology, , 62 (1 ) ,87-94 More Information

Wellmerling, Jack H; Chang, Sheng-Wei; Kim, Eunsoo; Osman, Wissam H; Boyaka, Prosper N; Borchers, Michael T; Cormet-Boyaka, Estelle (2019. ) Reduced expression of the Ion channel CFTR contributes to airspace enlargement as a consequence of aging and in response to cigarette smoke in mice.Respiratory research, , 20 (1 ) ,200 More Information

Contact Information

Academic - University of Cincinnati, Department of Internal Medicine, Medical Sciences Building
231 Albert Sabin Way, ML 0564
Cincinnati  Ohio, 45267
Phone: 513-558-4831
Fax: 513-558-4858
michael.borchers@uc.edu