UNIVERSITY OF WASHINGTON



January 1, 2009

Name: Lucas R. Hoffman, MD, PhD

Education:

1990 BS University of California, Berkeley

College of Chemistry

Berkeley, CA

1996 PhD University of California, Berkeley

College of Chemistry

Berkeley, CA

1998 MD University of California, San Francisco

School of Medicine

San Francisco, CA

Postgraduate Training:

2001-2005 Fellowship in Pediatric Pulmonology, Children’s Hospital

and Regional Medical Center, Seattle, WA

1998-2001 Residency in Pediatrics, Children's Hospital and Regional

Medical Center, Seattle, WA

Faculty Positions Held:

2007-present Assistant Professor in Pediatrics, Children’s Hospital and Regional Medical Center, Seattle, WA (now Seattle Children’s Hospital)

2005-2007 Acting Assistant Professor in Pediatrics, Children’s Hospital and

Regional Medical Center, Seattle, WA

2004-2005 Acting Instructor in Pediatrics, Children’s Hospital and

Regional Medical Center, Seattle, WA

Hospital Positions Held: None.

Honors:

2007 ICAAC (Interscience Conference on Antimicrobial Agents and Chemotherapy) Young Investigator Award from the American Society of Microbiology:

2006. First author of one of 2005’s “Top Articles in Infectious Disease” as judged by Pediatric News:



2004-2005 Leroy Matthews Physician Scientist Award

2004 Children’s Hospital and Regional Medical Center Fellows Research Day Presentation Award

2003-2004 Cystic Fibrosis Foundation Third-year Research Fellowship Training Award

2002-2003 Cystic Fibrosis Foundation Clinical Fellowship Second-year Training Award

2001-2002 Cystic Fibrosis Foundation Clinical Fellowship First-year Training Award

1996. Young Scientist Award for the meeting Options for the Control of Influenza III, Cairns, Australia

1994. Richard Fineberg Memorial Student Teaching Award, UCSF

1990-1998 Medical Scientist Training Program Award

1990 University Citation, UC Berkeley (One of top 10 Univ. grads)

Departmental Citation (valedictorian), College of Chemistry,

UC Berkeley

Invited graduation speaker

1988-1990 Thompson Chemistry Scholarship

Howard Chemistry Scholarship

1988 Phi Beta Kappa (Junior year)

1986-1990 Regents' Scholarship, UC Berkeley

Board Certification: Pediatric Pulmonology, American Board of Pediatrics, 2006.

General Pediatrics, American Board of Pediatrics, 2001.

Current License(s) to Practice: Washington State full license, number 025209MD00040283 Issued 8/8/01, expires 1/12/10

Professional Organizations:

American Academy of Pediatrics

American Association for the Advancement of Science

American Society for Microbiology

Society for Pediatric Research

American Thoracic Society

Teaching Responsibilities:

2008 Laboratory/research mentor for Dr. Daniel Wolter, a UW postdoctoral fellow in

the Hoffman laboratory (Pediatrics)

2006 Laboratory/research co-mentor for Doris Luk, a UW graduate student in Microbiology

2005-2007 Laboratory/research co-mentor for Danielle Elliott, a UW undergraduate pre-medical student

2002-2008 One one-hour lecture per lecture series for UW course “NURS 517”

2002-2008 Two one-hour lectures per lecture series for UW course “Rehab 400: Medical Sciences”

2001 Assistant Chief Resident in Pediatrics, Children’s Hospital and Regional Medical Center, Seattle, WA

1994 Teaching assistant for Macromolecular Interactions, Department of Pharmaceutical Chemistry, UCSF

Editorial Responsibilities: None.

Special National Responsibilities: None

Special Local Responsibilities:

2009-present Seattle Children’s Hospital Intern Retreat Faculty Committee

2008-present Children’s Hospital Pharmacy and Therapeutics Committee

2006-2008 Committee for Work/Life Balance, Childcare/Eldercare subgroup (Amy Carter, subgroup leader)

2004-present Working Group on Empyema, Children’s Hospital and Regional Medical Center, Seattle, WA

Research Funding:

Leroy Matthews Physician Scientist (career development) Award Renewal

Project number HOFFMA04L0

PI: Lucas Hoffman Sponsor: Samuel I. Miller

Approved, funding delayed to coincide with end of K08

Source: Cystic Fibrosis Foundation

Title: Alteration of Pseudomonas aeruginosa gene expression by sublethal cationic antibiotic concentrations: Adaptation to the CF airway.

Dates of approval: July 1, 2008- June 30, 2010

Annual direct cost: $85,000

CFF/NIH Award

Project number HOFFMA07P0

PI: Lucas Hoffman

Active Source: Cystic Fibrosis Foundation

Title: Bridge Funding to Develop Methods to Study Polymicrobial Community Interactions in Cystic Fibrosis Lung Disease

Dates of approval: January 1, 2008-December 31, 2009

Annual direct cost: $75,000

American Thoracic Society/Cystic Fibrosis Foundation Research Grant

Project number CF-07-003

PI: Lucas Hoffman

Active Source: The American Thoracic Society

Title: The Impact of S. aureus normal and SCV forms in Cystic Fibrosis Lung Disease

Dates of approval: January 1, 2008-December 31, 2009

Annual direct cost: $50,000

Institute of Translational Health Sciences Pilot Project

PI: Lucas Hoffman

Pending Source: ITHS

Title: Community-level physiologic profiling: A novel method to characterize polymicrobial infectious diseases.

Dates of requested support (award pending): January 1, 2009-December 31, 2009

Annual direct costs requested: $10,000

Mentored Clinical Scientist Development Award (K08)

PI: Lucas Hoffman Sponsor: Samuel I. Miller

Completed

Source: NIH, National Institute of Allergy and Infectious Disease

Title: Antibiotic-mediated adaptation of Pseudomonas aeruginosa.

Dates of support: July 15, 2005-May 31, 2008, no-cost extension until May 31, 2009

Annual direct cost: $116,950

Leroy Matthews Physician Scientist (career development) Award

Project number HOFFMA04L0

PI: Lucas Hoffman Sponsor: Samuel I. Miller

Completed Source: Cystic Fibrosis Foundation

Title: Alteration of Pseudomonas aeruginosa gene expression by sublethal cationic antibiotic concentrations: Adaptation to the CF airway.

Dates of approval: July 1, 2004- June 30, 2005

Annual direct cost: $67,500

Title: Cystic Fibrosis Foundation Third-year Research Fellowship Training Award

PI: Lucas Hoffman – Sponsor: Samuel Miller

Completed Source: Cystic Fibrosis Foundation

Dates: July 1, 2003 – June 30, 2004

Annual direct costs: $62,600

Title: Cystic Fibrosis Foundation Second-year Research Fellowship Training Award

PI: Lucas Hoffman – Sponsor: Samuel Miller

Completed Source: Cystic Fibrosis Foundation

Dates: July 1, 2002 – June 30, 2003

Annual direct costs: $43,750

Title: Cystic Fibrosis Foundation First Year Research Fellowship Training Award

PI: Lucas Hoffman – Sponsor: Samuel Miller

Completed Source: Cystic Fibrosis Foundation

Dates: July 1, 2001 – June 30, 2002

Annual direct costs: $42,000

Bibliography

Manuscripts in Refereed Journals

1. Stearns, DM; Hoffman, LR; and Armstrong, WH. Structure of N,N-[Bis(2-pyridylmethyl)-gamma-aminobutyrato]copper (II) Bromide Methanol Solvate. Acta Crystallographica Section C- Crystal Structure Communications, 1992. V48 FEB: 253-256.

2. Hoffman, LR. The Low pH-induced Conformational Change in the Influenza Hemagglutinin: Inhibitor Design. 1996. PhD thesis, UCSF.

3. Hernandez, LD; Hoffman, LR; Wolfsberg, TG; and White, JM. Virus-Cell and Cell-Cell Fusion. Annual Review of Cell and Developmental Biology, 1996. 12:627-661.

4. Hoffman, LR; Kuntz, ID; and White, JM. Structure-based Identification of an Inducer of the Low-pH Conformational Change in the Influenza Hemagglutinin: Irreversible Inhibition of Infectivity. Journal of Virology, 1997. 71(11):8808-8820.

5. Rutenber, EE; De Voss, JJ; Hoffman, LR; Stroud, RM; Lee, KH; Alvarez, J; McPhee, F; Craik, C; and Ortiz de Montellano, PR. The Discovery, Characterization, and Crystallographically Determined Binding Mode of an FMOC Containing Inhibitor of HIV-1 Protease. Bioorganic and Medicinal Chemistry, 1997. 5(7): 1311-1320.

6. Quiao, H; Pelletier, SL; Hoffman, LR; Hacker, J; Armstrong, RT; and White, JM. A Specific Proline Substitution in the Coiled-Coil Region of the Influenza Hemagglutinin Impairs its Membrane Fusion Activity. Journal of Cell Biology, 1998. 141(6):1335-1347.

7. Hoffman LR; D'Argenio DA; MacCoss MJ; Zhang Z; Jones RA; Miller SI; Aminoglycoside Antibiotics Induce Bacterial Biofilm Formation. Nature, 2005. 436(7054):1171-5.

8. Hoffman, LR*; Yen, YH*; Gibson, RL; Van Niel, CW. Lipoid Pneumonia due to Mexican Folk Remedies: Cultural Barriers to Diagnosis. Archives of Pediatrics and Adolescent Medicine, 2005. 159:1043-1048. *These two authors contributed equally.

9. Smith, EE; Buckley, DG; Wu, Z; Saenphimmachak, C; Hoffman, LR; D’Argenio, DA; Miller, SI; Ramsey, BW; Speert, DP; Moskowitz, SM; Burns, JL; Kaul, R; Olson, MV. Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc. Natl Acad. Sci. 2006. 103:8487-92.

10. Hoffman, LR; Miller, SI. The systems biology of infection in animal models bears fruit. Proc. Natl. Acad. Sci. USA, 2006. 103:9377-8.

11. Hoffman, LR; Déziel, E; D’Argenio, DA; Lépine, F; Emerson, J; McNamara, S; Gibson, RL; Ramsey, BW; Miller, SI. Selection for Staphylococcus aureus small-colony variants due to growth in the presence of Pseudomonas aeruginosa. Proc. Natl. Acad. Sci. USA, 2006. 103(52):19890-5.

12. D'Argenio DA*; Wu M*; Hoffman LR, Kulasekara HD, Deziel E, Smith EE, Nguyen H, Ernst RK, Larson Freeman TJ, Spencer DH, Brittnacher M, Hayden HS, Selgrade S, Klausen M, Goodlett DR, Burns JL, Ramsey BW, Miller SI. Growth phenotypes of Pseudomonas aeruginosa lasR mutants adapted to the airways of cystic fibrosis patients. Mol Microbiol. 2007. 64(2):512-33. *These two authors contributed equally.

13. Hoffman, LR; D’Argenio, DA; Bader, MW; Miller, SI. Microbial recognition of antibiotics: Ecological, physiological, and therapeutic implications. Microbe. 2007. 2(4):175-182.

14. Miller, SI; Hoffman, LR, Sanowar, S. Did bacterial sensing of host environments evolve from sensing within microbial communities? Cell Host Microbe. 2007. 1(2):85-7.

15. Hoffman, LR; Kulasekara, HD; Emerson, J; Houston, LS; Burns, JL; Ramsey, BW; and Miller, SI. Pseudomonas aeruginosa lasR mutants are associated with cystic fibrosis lung disease progression. J. Cyst. Fibros. 2009 Jan;8(1):66-70. Epub Oct., 2008.

Book Chapters

1. Hoffman, LR; White, JM; and Kuntz, ID. Fusion Mechanism of the Influenza Hemagglutinin: Inhibitor Design. In: Options for the Control of Influenza III: Proceedings. Brown, LE; Hampson, AW; and Webster, RG; eds. 1996. Elsevier Science, BV, The Netherlands.

2. White, JM; Hoffman, LR; Arevalo, JH; and Wilson, IA. Attachment and Entry of Influenza Virus into Host Cells: Pivotal Roles of the Hemagglutinin. In: Structural Biology of Viruses, Chiu,W; Burnett, RM; and Garcea, RL; eds. 1997. Oxford Press, New York.

Published Books, Videos, Software, etc.

None.

Other Publications, e.g., in Non-refereed Journals and Letters to the Editor

Hoffman, LR. How aspirin works. On website: How Stuff Works, .

Manuscripts Submitted or In Press

1. Hoffman, LR; Richardson, AR; Houston, LS; Kulasekara, HD; Martens-Habbena, W; Klausen, M; Burns, JL; Stahl, DO; Hassett, D; Fang, F; and Miller, SI. Nutrient availability as a mechanism for selection of antibiotic tolerant Pseudomonas aeruginosa within the CF airway. Submitted to Proceedings of the National Academy of Sciences, January 22, 2009, in editorial review.

2. Burns, JL; Emerson, J; Blackledge, M; Ramsey, BW; Hoffman, LR; and Gibson, RL. Changes in airway microbiology in a single CF center, 2001-2007. Submitted to the Journal of Cystic Fibrosis, February 4, 2009, under consideration.

Abstracts and Posters:

1. Hoffman, LR; Emerson, J; Gibson, RL; Redding, GJ. Frequency of Return to Best PFT Baseline After CF Cleanout: A Pilot Quality Improvement (QI) Project. Presented at: 2003 American Thoracic Society International Conference in Seattle, Washington, May 21, 2003. Am J Resp Crit Care Med, 2003. 167(7): 23.

2. Debley, JS; Hoffman, L; Redding, G. Thoracic Index as a Measure of Hyperinflation during and Following RSV Hospitalization. Presented at: 2003 ATS International Conference in Seattle, Washington, May 19, 2003. Am J Resp Crit Care Med, 2003. 167(7): 507.

3. Hoffman, LR; D’Argenio, D; Jacobs, M; Miller, SI. The response of Pseudomonas aeruginosa to sublethal tobramycin concentrations. Presented at: 2004 Williamsburg Conference on Cystic Fibrosis in Williamsburg, VA, June 6, 2004.

4. Hoffman LR; D’Argenio D; Ernst RK; Miller SI. Effect of the antibiotic tobramycin on biofilm formation by Pseudomonas aeruginosa. Presented at: 2004 Gordon Conference on Bacterial Cell Surfaces in New London, NH, June 28, 2004.

5. Hoffman LR; D'Argenio DA; MacCoss MJ; Zhang Z; Jones RA; Miller SI; Aminoglycoside Antibiotics Induce Bacterial Biofilm Formation. Presented at: 2005 Williamsburg Conference on Cystic Fibrosis in Williamsburg, VA, June 6, 2005.

6. Hoffman LR; D'Argenio DA; MacCoss MJ; Zhang Z; Jones RA; Miller SI; Aminoglycoside Antibiotics Induce Bacterial Biofilm Formation. Presented at: 2005 International Meeting on Pseudomonas in Marseille, France, August 26, 2005.

7. Hoffman LR; Déziel E; D’Argenio DA; Lépine F; Emerson J; McNamara S; Gibson RL; Ramsey BW; Miller SI. The Pseudomonas aeruginosa quinoline antibiotic HQNO selects antibiotic-resistant Staphylococcus aureus small-colony variants. Presented at: 2007 International Meeting on Pseudomonas in Seattle, Washington, August 28, 2007.

National Invitational Lectures, etc.

1. Fusion Mechanism of the Influenza Hemagglutinin: Inhibitor Design. At: The World Health Organization: Options for the Control of Influenza III; Cairns, Australia. May 4-9, 1996.

2. Preliminary Structure-based Searches for RSV/HIV Integrase Inhibitors. At: The Tenth Meeting of Groups Studying the Structure of AIDS-related Systems and Their Application to Targeted Drug Design; NIH campus, Bethesda, Maryland. June 25-27, 1996.

3. Case Presentation: Refractory Mycobacterial Pulmonary Infection in a Patient With Cystic Fibrosis. At: Seattle CF Center and Affiliate Centers Annual Clinical Conference, University of Washington, Seattle, Washington. July 19, 2002. And at: The 16th Annual North American CF Conference (NACFC), New Orleans, LA October 4, 2002.

4. Sublethal Tobramycin Concentrations Alter Pseudomonas aeruginosa Virulence and Biofilm Formation. At: Children’s Hospital and Regional Medical Center Fellows’ Research Day. April 20, 2004.

5. Return to Best Spirometric Baseline After Admission for CF Exacerbation. At: Seattle CF Center and Affiliate Centers Annual Clinical Conference, University of Washington, Seattle, Washington. July 15, 2004.

6. Antibiotic Induction of Pseudomonas aeruginosa Biofilm Formation. At: University of Washington Inderdepartmental Microbial Pathogenesis Seminar. December 9, 2004.

7. Cyclic di-GMP Regulation in Pseudomonas aeruginosa Biofilms. At: American Society for Microbiology 106th General Meeting, Orlando, Florida. May 24, 2006.

8. Pseudomonas-Staphylococcus antagonism: Small Colony Variants. At: Seattle CF Center and Affiliate Centers Annual Clinical Conference, University of Washington, Seattle, Washington. July 7, 2006.

9. Two Patients With Cystic Fibrosis. At: Department of Medicine Grand Rounds, University of Washington, Seattle, Washington. October 26, 2006.

10. Polymicrobial Interactions, Presenter and Roundtable Discussion Moderator. 2007 North American Cystic Fibrosis Foundation Conference, Anaheim, California, October 6, 2007.

11. Pseudomonas-Staphylococcus molecular interactions impact antibiotic susceptibility and respiration in both species. (Symposium Chair and speaker) At: The 22nd Annual North American CF Conference (NACFC), Orlando, FL, October 26, 2008.

12. Bacterial Adaptation During Chronic Infections: Lessons from Cystic Fibrosis. At: University of Virginia Microbiology Departmental Seminar, Charlottesville, Virginia. May 14, 2008.

Languages Spoken:

Fluent in Spanish, working knowledge of Russian and German.

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2/6/09- LRH

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