Roberto Adachi, MD
Department of Pulmonary Medicine, Division of Internal Medicine
Present Title & Affiliation
Primary Appointment
Professor, Department of Pulmonary Medicine, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
Dual/Joint/Adjunct Appointment
Adjunct Professor, TEC Monterrey School of Medicine, Monterrey
Research Interests
Mast cells are important components of innate and adaptive immune responses. Upon activation they secrete a variety of preformed inflammatory mediators via regulated exocytosis, newly synthesized cytokines and chemokines via constitutive exocytosis, and prostaglandins and leukotrienes using a transmembrane transport. My main interest is to study regulated exocytosis in mast cells, in particular the role of Syntaxins, Synaptotagmins, Munc13 and Munc18 proteins in this phenomenon. In the process we have generated a variety of mutant mice and we are studying the consequences of defective mast cell regulated exocytosis in models of inflammation and infection. I am also interested in the cargo released by mast cells via regulated exocytosis, and I am studying the effects of the proteases mMCP‑5, 6 and 7 in inflammation, defense against infections and tumorogenesis.
Education & Training
Degree-Granting Education
| 1990 | Cayetano Heredia Peruvian University, Lima, PER, MD, Medicine |
Postgraduate Training
| 1997-1998 | Research Fellowship, Molecular Biology, Baylor College of Medicine, Houston, TX |
| 1994-1997 | Clinical Fellowship, Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX |
| 1991-1994 | Residency, Internal Medicine, Henry Ford Hospital, Detroit, MI |
Board Certifications
| 1997 | Critical Care Medicine |
| 1996 | Pulmonary Medicine |
| 1994 | Internal Medicine |
Experience & Service
Academic Appointments
Associate Faculty, Graduate School of Biomedical Sciences, Texas A & M University Health Science Center, Houston, TX, 2007 - 2020
Adjunct Faculty, Institute of Biosciences and Technology, Texas A & M University Health Science Center, Houston, TX, 2006 - 2020
Assistant Professor, Department of Critical Care Medicine, Division of Anesthesiology, Critical Care Medicine and Pain Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 2003 - 2007
Assistant Professor, Department of Pulmonary Medicine, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 2003 - 2011
Staff Physician, Department of Pulmonary and Critical Care Medicine, Division of Medical Care Line, Houston VA Medical Center, Houston, TX, 1998 - 2003
Assistant Professor, Department of Medicine, Baylor College of Medicine, Houston, TX, 1998 - 2005
Honors & Awards
| 2007 | Research Award, Michael and Mariet Cyrus Scholar |
| 2001 | Attending of the Year, Baylor College of Medicine |
| 2001 | Advanced Research Career Award, Veterans Administration |
| 2000 | Merit Review Award, Veterans Administration |
| 2000 | Research Award, American Heart Association |
| 1999 | Research Award, Caroline Weiss Law Fund for Research in Molecular Medicine |
| 1998 | Outstanding Research Project, Texas Thoracic Society |
| 1996 | Research Award, Foundation for Fellows in Asthma Research |
| 1994 | Best Senor Resident, Henry Ford Hospital, Department of Internal Medicine |
| 1990 | Graduated in First Place, Summa Cum Laude, Cayetano Heredia Peruvian University Medical School |
| 1981 | Graduated in First Place, Summa Cum Laude, La Inmaculada College |
Selected Publications
Peer-Reviewed Articles
- Roy MG, Livraghi-Butrico A, Fletcher AA, McElwee MM, Evans SE, Boerner RM, Alexander SN, Bellinghausen LK, Song AS, Petrova YM, Tuvim MJ, Adachi R, Romo I, Bordt AS, Bowden MG, Sisson JH, Woodruff PG, Thornton DJ, Rousseau K, De la Garza MM, Moghaddam SJ, Karmouty-Quintana H, Blackburn MR, Drouin SM, Davis CW, Terrell KA, Grubb BR, O'Neal WK, Flores SC, Cota-Gomez A, Lozupone CA, Donnelly JM, Watson AM, Hennessy CE, Keith RC, Yang IV, Barthel L, Henson PM, Janssen WJ, Schwartz DA, Boucher RC, Dickey BF, Evans CM. Muc5b is required for airway defence. Nature 505(7483):412-6, 2014. e-Pub 2013. PMID: 24317696.
- Cleaver JO, You D, Michaud DR, Pruneda FA, Juarez MM, Zhang J, Weill PM, Adachi R, Gong L, Moghaddam SJ, Poynter ME, Tuvim MJ, Evans SE. Lung epithelial cells are essential effectors of inducible resistance to pneumonia. Mucosal Immunol 7(1):78-88, 2014. e-Pub 2013. PMID: 23632328.
- Johnson SL, Wedemeyer C, Vetter DE, Adachi R, Holley MC, Elgoyhen AB, Marcotti W. Cholinergic efferent synaptic transmission regulates the maturation of auditory hair cell ribbon synapses. Open Biol 3(11):130163, 2013. PMID: 24350389.
- Magarinos NJ, Bryant KJ, Fosang AJ, Adachi R, Stevens RL, McNeil HP. Mast cell-restricted, tetramer-forming tryptases induce aggrecanolysis in articular cartilage by activating matrix metalloproteinase-3 and -13 zymogens. J Immunol 191(3):1404-12, 2013. e-Pub 2013. PMID: 23797671.
- Beckett EL, Stevens RL, Jarnicki AG, Kim RY, Hanish I, Hansbro NG, Deane A, Keely S, Horvat JC, Yang M, Oliver BG, van Rooijen N, Inman MD, Adachi R, Soberman RJ, Hamadi S, Wark PA, Foster PS, Hansbro PM. A new short-term mouse model of chronic obstructive pulmonary disease identifies a role for mast cell tryptase in pathogenesis. J Allergy Clin Immunol 131(3):752-762, 2013. e-Pub 2013. PMID: 23380220.
- Kim K, Petrova YM, Scott BL, Nigam R, Agrawal A, Evans CM, Azzegagh Z, Gomez A, Rodarte EM, Olkkonen VM, Bagirzadeh R, Piccotti L, Ren B, Yoon JH, McNew JA, Adachi R, Tuvim MJ, Dickey BF. Munc18b is an essential gene in mice whose expression is limiting for secretion by airway epithelial and mast cells. Biochem J 446(3):383-94, 2012. e-Pub 2012. PMID: 22694344.
- Adachi R, Krilis SA, Nigrovic PA, Hamilton MJ, Chung K, Thakurdas SM, Boyce JA, Anderson P, Stevens RL. Ras guanine nucleotide-releasing protein-4 (RasGRP4) involvement in experimental arthritis and colitis. J Biol Chem 287(24):20047-55, 2012. e-Pub 2012. PMID: 22511759.
- Prieto-García A, Zheng D, Adachi R, Xing W, Lane WS, Chung K, Anderson P, Hansbro PM, Castells M, Stevens RL. Mast cell restricted mouse and human tryptase·heparin complexes hinder thrombin-induced coagulation of plasma and the generation of fibrin by proteolytically destroying fibrinogen. J Biol Chem 287(11):7834-44, 2012. e-Pub 2012. PMID: 22235124.
- Zhang J, Sun J, Lindholt JS, Sukhova GK, Sinnamon M, Stevens RL, Adachi R, Libby P, Thompson RW, Shi GP. Mast cell tryptase deficiency attenuates mouse abdominal aortic aneurysm formation. Circ Res 108(11):1316-27, 2011. e-Pub 2011. PMID: 21493897.
- Hamilton MJ, Sinnamon MJ, Lyng GD, Glickman JN, Wang X, Xing W, Krilis SA, Blumberg RS, Adachi R, Lee DM, Stevens RL. Essential role for mast cell tryptase in acute experimental colitis. Proc Natl Acad Sci U S A 108(1):290-5, 2011. e-Pub 2010. PMID: 21173247.
- Younan G, Suber F, Xing W, Shi T, Kunori Y, Abrink M, Pejler G, Schlenner SM, Rodewald HR, Moore FD, Stevens RL, Adachi R, Austen KF, Gurish MF. The inflammatory response after an epidermal burn depends on the activities of mouse mast cell proteases 4 and 5. J Immunol 185(12):7681-90, 2010. e-Pub 2010. PMID: 21076070.
- Wu XS, McNeil BD, Xu J, Fan J, Xue L, Melicoff E, Adachi R, Bai L, Wu LG. Ca(2+) and calmodulin initiate all forms of endocytosis during depolarization at a nerve terminal. Nat Neurosci 12(8):1003-10, 2009. e-Pub 2009. PMID: 19633667.
- Melicoff E, Sansores-Garcia L, Gomez A, Moreira DC, Datta P, Thakur P, Petrova Y, Siddiqi T, Murthy JN, Dickey BF, Heidelberger R, Adachi R. Synaptotagmin-2 controls regulated exocytosis but not other secretory responses of mast cells. J Biol Chem 284(29):19445-51, 2009. e-Pub 2009. PMID: 19473977.
- He L, Xue L, Xu J, McNeil BD, Bai L, Melicoff E, Adachi R, Wu LG. Compound vesicle fusion increases quantal size and potentiates synaptic transmission. Nature 459(7243):93-7, 2009. PMID: 19279571.
- Tuvim MJ, Mospan AR, Burns KA, Chua M, Mohler PJ, Melicoff E, Adachi R, Ammar-Aouchiche Z, Davis CW, Dickey BF. Synaptotagmin 2 couples mucin granule exocytosis to Ca2+ signaling from endoplasmic reticulum. J Biol Chem 284(15):9781-7, 2009. e-Pub 2009. PMID: 19208631.
- Shin K, Nigrovic PA, Crish J, Boilard E, McNeil HP, Larabee KS, Adachi R, Gurish MF, Gobezie R, Stevens RL, Lee DM. Mast cells contribute to autoimmune inflammatory arthritis via their tryptase/heparin complexes. J Immunol 182(1):647-56, 2009. PMID: 19109198.
- McNeil HP, Shin K, Campbell IK, Wicks IP, Adachi R, Lee DM, Stevens RL. The mouse mast cell-restricted tetramer-forming tryptases mouse mast cell protease 6 and mouse mast cell protease 7 are critical mediators in inflammatory arthritis. Arthritis Rheum 58(8):2338-46, 2008. PMID: 18668540.
- Clement CG, Evans SE, Evans CM, Hawke D, Kobayashi R, Reynolds PR, Moghaddam SJ, Scott BL, Melicoff E, Adachi R, Dickey BF, Tuvim MJ. Stimulation of lung innate immunity protects against lethal pneumococcal pneumonia in mice. Am J Respir Crit Care Med 177(12):1322-30, 2008. e-Pub 2008. PMID: 18388354.
- Katsoulotos GP, Qi M, Qi JC, Tanaka K, Hughes WE, Molloy TJ, Adachi R, Stevens RL, Krilis SA. The diacylglycerol-dependent translocation of Ras guanine nucleotide-releasing protein 4 inside a human mast cell line results in substantial phenotypic changes, including expression of interleukin 13 receptor alpha2. J Biol Chem 283(3):1610-21, 2008. e-Pub 2007. PMID: 18024961.
- Bashoura L, Gupta S, Jain A, Couriel DR, Komanduri KV, Eapen GA, Safdar A, Broglio KR, Adachi R, Dickey BF. Inhaled corticosteroids stabilize constrictive bronchiolitis after hematopoietic stem cell transplantation. Bone Marrow Transplant 41(1):63-7, 2008. e-Pub 2007. PMID: 17934530.
- Sun J, Pang ZP, Qin D, Fahim AT, Adachi R, Südhof TC. A dual-Ca2+-sensor model for neurotransmitter release in a central synapse. Nature 450(7170):676-82, 2007. PMID: 18046404.
- Young HW, Williams OW, Chandra D, Bellinghausen LK, Pérez G, Suárez A, Tuvim MJ, Roy MG, Alexander SN, Moghaddam SJ, Adachi R, Blackburn MR, Dickey BF, Evans CM. Central role of Muc5ac expression in mucous metaplasia and its regulation by conserved 5' elements. Am J Respir Cell Mol Biol 37(3):264-72, 2007. e-Pub 2007. PMID: 17463395.
- Thakurdas SM, Melicoff E, Sansores-Garcia L, Moreira DC, Petrova Y, Stevens RL, Adachi R. The mast cell-restricted tryptase mMCP-6 has a critical immunoprotective role in bacterial infections. J Biol Chem 282(29):20809-15, 2007. e-Pub 2007. PMID: 17456473.
- Pang ZP, Melicoff E, Padgett D, Liu Y, Teich AF, Dickey BF, Lin W, Adachi R, Südhof TC. Synaptotagmin-2 is essential for survival and contributes to Ca2+ triggering of neurotransmitter release in central and neuromuscular synapses. J Neurosci 26(52):13493-504, 2006. PMID: 17192432.
- Yasuda S, Morokawa N, Wong GW, Rossi A, Madhusudhan MS, Sali A, Askew YS, Adachi R, Silverman GA, Krilis SA, Stevens RL. Urokinase-type plasminogen activator is a preferred substrate of the human epithelium serine protease tryptase epsilon/PRSS22. Blood 105(10):3893-901, 2005. e-Pub 2005. PMID: 15701722.
- Nigam R, Sepulveda J, Tuvim M, Petrova Y, Adachi R, Dickey BF, Agrawal A. Expression and transcriptional regulation of Munc18 isoforms in mast cells. Biochim Biophys Acta 1728(1-2):77-83, 2005. PMID: 15777698.
- Zhang BM, Kohli V, Adachi R, López JA, Udden MM, Sullivan R. Calmodulin binding to the C-terminus of the small-conductance Ca2+-activated K+ channel hSK1 is affected by alternative splicing. Biochemistry 40(10):3189-95, 2001. PMID: 11258935.
- Agrawal A, Adachi R, Tuvim M, Yan XT, Teich AH, Dickey BF. Gene structure and promoter function of murine Munc18-2, a nonneuronal exocytic Sec1 homolog. Biochem Biophys Res Commun 276(3):817-22, 2000. PMID: 11027553.
- Adachi R, Nigam R, Tuvim MJ, DeMayo F, Dickey BF. Genomic organization, chromosomal localization and expression of the murine Rab3D gene. Biochem Biophys Res Commun 273(3):877-83, 2000. PMID: 10891340.
- Baram D, Adachi R, Medalia O, Tuvim M, Dickey BF, Mekori YA, Sagi-Eisenberg R. Synaptotagmin II negatively regulates Ca2+-triggered exocytosis of lysosomes in mast cells. J Exp Med 189(10):1649-58, 1999. PMID: 10330444.
- Tuvim MJ, Adachi R, Chocano JF, Moore RH, Lampert RM, Zera E, Romero E, Knoll BJ, Dickey BF. Rab3D, a small GTPase, is localized on mast cell secretory granules and translocates to the plasma membrane upon exocytosis. Am J Respir Cell Mol Biol 20(1):79-89, 1999. PMID: 9870920.
Invited Articles
- McNeil HP, Adachi R, Stevens RL. Mast cell-restricted tryptases: structure and function in inflammation and pathogen defense. J Biol Chem 282(29):20785-9, 2007. e-Pub 2007. PMID: 17504754.
- Stevens RL, Adachi R. Protease-proteoglycan complexes of mouse and human mast cells and importance of their beta-tryptase-heparin complexes in inflammation and innate immunity. Immunol Rev 217:155-67, 2007. PMID: 17498058.
- Tuvim MJ, Adachi R, Hoffenberg S, Dickey BF. Traffic control: Rab GTPases and the regulation of interorganellar transport. News Physiol Sci 16:56-61, 2001. PMID: 11390949.
Grant & Contract Support
| Title: | Mechanism and pathophysiological significance of mast cell regulated exocytosis |
| Funding Source: | NIH/NIAID |
| Role: | Principal Investigator |
| Title: | Mast cell tryptases in lung cancer development and progression |
| Funding Source: | Cancer Prevention & Research Institute of Texas (CPRIT) |
| Role: | Principal Investigator |
Patient Reviews
CV information above last modified December 15, 2023