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Roberto Adachi, MD

Present Title & Affiliation

Primary Appointment

Associate Professor, Department of Pulmonary Medicine, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX

Dual/Joint/Adjunct Appointment

Adjunct Faculty, Institute of Biosciences and Technology, Texas A & M University Health Science Center, Houston, TX
Associate Faculty, Graduate School of Biomedical Sciences, Texas A & M University Health Science Center, Houston, TX
Adjunct Professor, Tecnologico de Monterrey School of Medicine, Monterrey, Nuevo Leon, Mexico

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.

Office Address

The University of Texas MD Anderson Cancer Center
Institute of Biosciences and Technology
2121 W. Holcombe Blvd. 703D
Unit Number: 1100
Houston, TX 77030
Room Number: IBT 7.703
Phone: 713-563-0410
Fax: 713-563-0411

Education & Training

Degree-Granting Education

1990 Cayetano Heredia Peruvian University, Lima, Peru, MD, Cum Laude, Medicine

Postgraduate Training

7/1997-8/1998 Research Fellowship, Molecular Biology, Baylor College of Medicine, Houston, TX, Burton Dickey, MD
7/1994-6/1997 Clinical Fellowship, Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, Joseph Rodarte, MD
7/1991-6/1994 Residency, Internal Medicine, Henry Ford Hospital, Detroit, MI, Michael Leasch, MD

Board Certifications

9/2007 Critical Care Medicine
9/2006 Pulmonary Medicine
11/2004 Internal Medicine

Experience/Service

Academic Appointments

Assistant Professor, Department of Critical Care, Division of Anesthesiology and Critical Care, The University of Texas MD Anderson Cancer Center, Houston, TX, 11/2003-2/2007
Assistant Professor, Department of Pulmonary Medicine, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 10/2003-8/2011
Assistant Professor, Department of Medicine, Baylor College of Medicine, Houston, TX, 9/1998-6/2005
Staff Physician, Pulmonary and Critical Care Medicine, Medical Care Line, Houston VA Medical Center, Houston, TX, 9/1998-10/2003

Honors and Awards

2007 Research Award, Michael and Mariet Cyrus Scholar
2001 Advanced Research Career Award, Veterans Administration
2001 Attending of the Year, Baylor College of Medicine
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 Resident of the Year, Internal Medicine, Henry Ford Hospital
1990 Graduated in First Place, Cayetano Heredia Peruvian University
1981 Graduated in First Place, La Inmaculada College

Selected Publications

Peer-Reviewed Original Research Articles

1. 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, 1/4/2011. e-Pub 12/20/2010. PMCID: PMC3017166.
2. 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, 12/15/2010. e-Pub 11/12/2010. PMID: 21076070.
3. 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, 8/2009. e-Pub 7/2009. PMID: 19633667.
4. 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, 7/2009. e-Pub 5/2009. PMCID: PMC2740570.
5. 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, 5/2009. PMCID: PMC2768540.
6. 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, 4/2009. e-Pub 2/2009. PMCID: PMC2665099.
7. 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, 1/2009. PMCID: PMC2610352.
8. 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, 8/2008. PMID: 18668540.
9. 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, 6/2008. e-Pub 4/2008. PMCID: PMC2427056.
10. 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, 1/2008. e-Pub 10/2007. PMID: 17934530.
11. 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, 1/2008. e-Pub 11/2007. PMID: 18024961.
12. 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, 11/2007. PMID: 18046404.
13. 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, 9/2007. e-Pub 4/2007. PMCID: PMC1994232.
14. 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, 7/2007. e-Pub 4/2007. PMID: 17456473.
15. 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, 12/2006. PMID: 17192432.
16. 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, 5/2005. e-Pub 2/2005. PMCID: PMC1895090.
17. 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, 4/2005. PMID: 15777698.
18. 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, 3/2001. PMID: 11258935.
19. 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, 10/2000. PMID: 11027553.
20. 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, 7/2000. PMID: 10891340.
21. 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, 5/1999. PMCID: PMC2193646.
22. 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, 1/1999. PMID: 9870920.

Invited Articles

1. 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, 7/2007. e-Pub 5/2007. PMID: 17504754.
2. 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, 6/2007. PMID: 17498058.
3. Tuvim MJ, Adachi R, Hoffenberg S, Dickey BF. Traffic control: Rab GTPases and the regulation of interorganellar transport. News Physiol Sci 16:56-61, 4/2001. PMID: 11390949.

Grant & Contract Support

Title: Mechanism and pathophysiological significance of mast cell regulated exocytosis
Funding Source: NIH/NIAID
Role: Principal Investigator
Duration: 3/1/2011 - 2/29/2016
 
Title: Mast cell tryptases in lung cancer development and progression
Funding Source: Cancer Prevention & Research Institute of Texas (CPRIT)
Role: Principal Investigator
Duration: 1/1/2011 - 6/30/2014

Last updated: 7/11/2014