SUMMARY STATEMENT

PROGRAM CONTACT: ( Privileged Communication ) Release Date: 12/02/2016

Revised Date:

Application Number: 1 K08 AI130357-01

Principal Investigator 

LU, LENETTE

Applicant Organization: MASSACHUSETTS GENERAL HOSPITAL

Review Group: MID-B 

Microbiology and Infectious Diseases B Subcommittee 

MID-B November 2016

Meeting Date: 11/04/2016 RFA/PA: PA16-191

Council: JAN 2017 PCC: M33 B

Requested Start: 04/01/2017

Dual IC(s): HL

Project Title: Antibody Mediated Mechanisms of Immune Modulation in Tuberculosis

SRG Action: Impact Score:

Next Steps: Visit http://grants.nih.gov/grants/next_steps.htm

Human Subjects: 30-Human subjects involved - Certified, no SRG concerns

Animal Subjects: 10-No live vertebrate animals involved for competingappl.

Gender: 1A-Both genders, scientifically acceptable

Minority: 1A-Minorities and non-minorities, scientifically acceptable 

Children: 3A-No children included, scientifically acceptable

Clinical Research - not NIH-defined Phase IIITrial

Project Direct Costs Estimated

Year Requested Total Cost 

1 

2 

3 

4 

5 

TOTAL

ADMINISTRATIVE BUDGET NOTE: The budget shown is the requested budget and has not been adjusted 

to reflect any recommendations made by reviewers. If an award is planned, the costs will be calculated by 

Institute grants management staff based on the recommendations outlined below in the COMMITTEE 

BUDGET RECOMMENDATIONS section.

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1 K08 AI130357-01 2 MID-B 

LU, L 

1K08AI130357-01 Lu, L 

RESUME AND SUMMARY OF DISCUSSION: This exceptional new application for a Mentored Clinical 

Scientist Research Career Development Award (K08) entitled “Antibody Mediated Mechanisms of 

Immune Modulation in Tuberculosis” was submitted by Lenette Lu, MD/PhD from Massachusetts 

General Hospital. 

The goal of this K08 submission is to provide the applicant with a career development/training 

opportunity while focusing on the potential contribution of humoral immunity to the control of M. 

tuberculosis in humans. The application is based on a first author publication recently accepted by 

Cell. In this K08 application she proposes to probe potential mechanisms that might account for a 

protective effect she has observed with certain antibodies in patients with contained (latent) M. 

tuberculosis infection that are not present in patients with uncontrolled disease. She notes that while 

neutralizing antibodies to M. tuberculosis do not correlate with protection, she has presented evidence 

that antibodies that recruit cellular responses might be important contributors to the immune response 

to this global pathogen. This application aims to unravel how Ab Fc domains contribute to immune 

protection against Mtb infection at the cellular level. The three aims are to 1) define the Ag specificity of 

functional Mtb specific Abs; 2) dissect the role of Fc/FcR mediated intracellular Mtb restriction and 3) 

identify macrophage effector mechanisms of Ab dependent intracellular Mtb restriction. 

Among strengths are the qualifications and experience of this superior candidate. She has received 

both an MD and PhD and has been well trained in global Tb work. Furthermore, she has been highly 

productive with several first author papers in high impact journals. The project of probing differential 

immune responses and the role of humoral immunity against M. tuberculosis is one of great 

significance to public health. The research plan is innovative and well supported by preliminary data. 

The mentoring team as well as the resources of the institution and institutional commitment are first rate 

and she has access to an important sample cohort. 

Minor weaknesses were identified in the research and career development plans. The panel questioned 

how patients with latent disease would be identified. Moreover, the career development plan lacks 

coursework in key areas such as host microbial interactions, host immunity or biostatistics, all critical to 

the application. However, the panel’s enthusiasm for this highly productive candidate with a 

commitment to TB research outweighed these weaknesses. Based upon the evaluation of scientific and 

technical merit, this application received an Overall Impact/Priority score of 17. 

DESCRIPTION (provided by applicant): 

Project Summary/Abstract This proposal presents a five year research career development program 

focused on the study of antibody mediated immune modulation in tuberculosis to expand the breadth 

and depth of understanding the role of humoral immunity in this disease. The candidate is currently an 

Instructor of Medicine at Harvard Medical School in the Division of Infectious Diseases at the 

Massachusetts General Hospital. The outlined proposal builds on the candidate's previous research 

and clinical experience in host pathogen interactions by integrating two new domains of expertise 

represented by her mentor team of Drs Sarah Fortune and Galit Alter at the Harvard School of Public 

Health and the Ragon Institute of MGH, MIT and Harvard: tuberculosis and antibody mediated 

mechanisms of innate immune effector functions. The proposed experiments and didactic work will 

position the candidate with a unique set of cross disciplinary skills that will enable her transition to 

independence as a physician scientist in antibody mediated host pathogen interactions in tuberculosis. 

One third of the world's population carries the burden of tuberculosis (TB). Efforts to reduce this burden 

have been hindered by the lack effective diagnostics and a protective vaccine underpinned by gaps in 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1 K08 AI130357-01 3 MID-B 

LU, L 

the understanding of the immune response in TB disease. While cellular immunity is important, the 

antibody (Ab) or humoral landscape is poorly understood. Ab function is determined by the combination 

of antigen specificity via the Fab and ability to recruit functional responses via the Fc domain. Ab Fc 

mediated recruitment of cellular responses is a promising underexplored potential for immune control. 

The foundation for this proposal is based on preliminary studies evaluating differences in antibody 

profiles from a systems serological approach in a cohort of individuals with latent and active TB that 

suggest a potential protective role for antibodies in TB disease. How exactly antibodies might function 

in this context and its physiological relevance are questions that this proposal begins to address. More 

specifically, the aims of this proposal are 1: Define the antigen specificity of functional M. tuberculosis 

(Mtb) specific antibodies, 2: Dissect the role for Fc/FcR mediated intracellular Mtb restriction and 3: 

Identify the macrophage effector mechanisms through which Ab restrict intracellular Mtb. The scientific 

objective of this proposal is to begin to define the Ab Fab and Fc features with the capacity to mediate 

effector function against intracellular Mtb with the vision of targeted transition into an appropriate animal 

model to generate hypotheses that inform the direction and design of subsequent human studies to 

expand the repertoire for immune correlates/diagnostics and rational vaccine design. 

PUBLIC HEALTH RELEVANCE 

Project Narrative One third of the world's population carries the burden of tuberculosis. Efforts to 

reduce this burden have been hindered by the lack effective diagnostics and a protective vaccine 

underpinned by gaps in the understanding of the immune response in tuberculosis disease. The 

proposed research will explore the role of humoral immunity in tuberculosis disease! with the vision that 

antibody features may be harnessed to expand the repertoire for immune correlates, diagnostics and 

rational vaccine design. 

CRITIQUE: The comments in the CRITIQUE section were prepared by the reviewers assigned to this 

application and are provided without significant modification or editing by staff. They are included to 

indicate the range of comments made during the discussion, and may not reflect the final outcome. The 

RESUME AND SUMMARY OF DISCUSSION section summarizes the final opinion of the committee 

after the discussion and is the basis for the assigned Impact/Priority score. 

Critique 1 

Candidate: 1 

Career Development 

Plan/Career Goals /Plan to 

Provide Mentoring: 

5 

Research Plan: 2 

Mentor(s), Co-Mentor(s), 

Consultant(s), 

Collaborator(s): 

1 

Environment Commitment 1 

to the Candidate: 

Overall Impact: 

This innovative K08 studies how Mtb specific antibody Fc mediated interactions may contribute to 

protection from active TB. Impact score is largely driven by the clear dedication of the applicant to TB 

pathogenesis evident from strong preliminary data for all proposed aspects of the application. The 
 

 

 

 

 

 

 

 

 

 

 

1 K08 AI130357-01 4 MID-B 

LU, L 

premise is based on intriguing preliminary serum studies in cohorts with latent and active TB, which 

have been recently been accepted for publication in Cell. The overall research approach is well 

rationalized and laid out with progressive analysis of several players in the Fc mediated pathway of Mtb 

restriction in macrophages. The team of mentors, advisors and collaborators, as well as the 

environment and local TB expertise are outstanding to successfully pursue the proposed studies. The 

innovative nature of the application based on clinical samples has excellent potential for future 

applications to small molecule or vaccine based therapeutics. The innovation and high impact potential 

of the application outweigh the very modest career development plan. 

1. Candidate: 

Strengths 

 The applicant is well trained in microbial pathogenesis, specifically virus host innate 

responses and more recently TB. After receiving her MD/PhD in 2010 from Case Western 

Reserve University School of Medicine, she completed her residency in Internal Medicine at 

Weill Cornell in 2013 and fellowship in infectious disease at Massachusetts General Hospital 

in 2015. She is presently a postdoctoral fellow and teachers assistant at Harvard School of 

Public Health. Her interest in clinical microbiology with a focus on TB and expertise in 

cellular host pathogen interactions provide an excellent background to expand her studies to 

antibody-Fc mediated mechanisms of protection from Tb. 

 Productivity is excellent with six primary authored publications, including one in J Biol Chem 

from her PhD, 4 clinical reports since 2010, and a recently accepted publication in Cell, 

which is the basis of the application. The studies on divergent humoral profiles in patients 

with different TB disease states and consequences for Mtb restriction accepted in ‘Cell’ are 

likely to have high impact. 

 During her residency the applicant gained experience in global health from rotations in 

Thailand, Haiti and Tanzania. 

 She was supported by a T32 training grant in the past 2 years (p92). 

 The referee letters are exceptionally laudatory, emphasizing the applicant’s passion for 

teaching and learning, thoughtfulness, intellectual vibrancy and extraordinary potential. 



Weaknesses 

 None noted 

2. Career Development Plan/ Career Goals & Objectives: 

Strengths 

 The long term goal is to pursue a career in infectious disease basic research to apply 

insights to patient care in resource limited areas. 



Weaknesses 

 A formal career development plan is lacking. The applicant lists progress in learning new 

skills in several areas during her present fellowship, but it is unclear how the KO8 

mechanism will be used to strengthen expertise in host microbial interactions at the cellular, 

host immunity or biostatistics, all critical to the application. 
 

 

 

 

 

1 K08 AI130357-01 5 MID-B 

LU, L 

 There are no plans for formal coursework in specialty areas critical to the application. Career 

development activities and training are also lacking. 

3. Research Plan: 

Strengths 

 The concept that antigen specific Ab plays a role in restricting Mtb infection via FcRs is 

largely unexplored and may lead to new strategies of vaccine design. This application aims 

to unravel how Ab Fc domains contribute to immune protection against Mtb infection at the 

cellular level. The three aims to 1) define the Ag specificity of functional Mtb specific Abs; 2) 

dissect the role of Fc/FcR mediated intracellular Mtb resytriction and 3) identify macrophage 

effector mechanisms of Ab dependent intracellular Mtb restriction, are well integrated and 

conceptually straightforward. 

 Preliminary data is supportive. It demonstrates that a link between distinct humoral serum 

signatures (Ag specificity, Ig subclass, FcR affinity, glycosylation state, FcR activity) with low 

and high bacterial burden also correlates with antimicrobial activity in an in vitro macrophage 

infection model. 

 Expansion of studies to an additional patient cohort is essential to validate preliminary 

findings using ATB and LTB patient cohorts from South Africa. 

 Approaches in aim 1 are well rationalized and promise to reveal extensive new insights into 

Ag specific Mtb humoral responses. Studies will characterize the spectrum of Ag specificity 

of IgG mediating protective FcR mediated function using MTb proteome array 

encompassing 4262 proteins (>95%). IgG activities will be assesssed using functional Fc 

signatures (e.g.ADCC) and validated via Ag mediated IgG depletion. 

 Aim 2 constitutes a best effort approach to identify the activating FcgRIIIa as the prominent 

FcR mediating intracellular Mtb restriction. Results are verified using complimentary 

knockdown, enzymatic, and microscopic approaches to interfere with FcR engagement. 

 Aim 3 linking phagosomal fusion and inflammasome activation as mechanisms contributing 

to intracellular Mtb control is critical to ultimately target specific pathways enhancing Mtb 

restriction. A variety of reagents and inhibitors will test the role of the IL-1b pathway and 

autophagy. While these pathways may be difficult to dissect, the expertise of the mentors 

and collaborators is expected to be invaluable for interpretation. 

 Biological resources are appropriately authenticated. 

Weaknesses 

 Aim 1: Fig. 2 indicates that IgG from normal serum provides protection similar to ATB 

derived IgG. Additional protection specifically by LTB derived IgG is significant, but less than 

40%. It is unclear how the apparent non specific protection is accounted for. Aim 1 also 

provides no strategy to prioritize between multiple possible Ag reactivities of IgG to vast 

amounts of Mtb proteins. 

 There are no efforts to take advantage of insights from aim 1 for studies in aims 2 and 3. 

4. Mentor(s), Co-Mentor(s), Consultant(s), Collaborator(s): 

Strengths 
 

 

 

 

 

 

1 K08 AI130357-01 6 MID-B 

LU, L 

 The mentor team is composed of Drs Fortune, MD, and Alter (PhD). Dr Fortune is an expert 

in studying mechanisms underlying heterogeneity in TB disease and treatment outcomes 

using genetics and high throughput technologies. Dr Alter complements Dr Fortunes 

expertise by studying innate immune responses to chronic viral infection and more recently 

antibody and Fc profiling in TB patients. This is a superb scientific team for the application’s 

success. 

 The scientific advisory committee including Drs Iwasaki, Nummerjahn and Batista, is headed 

by Dr Rubin, another expert in TB microbiology, with an excellent mentorship record. Their 

complementary expertise in innate immunity, inflammasome activation, FcR function, cell 

biology and microbiology, will be crucial in data interpretation and ongoing experimental 

design. 

 Dr Restrepo (Univ Texas) will be a resource for clinical samples and Dr. Hayden (MGH) will 

provide statistical support. 

 An extensive letter is provided by the mentors to support and monitor the candidate’s 

progress at all levels (p105). 

Weaknesses 

 None noted 

5. Environment and Institutional Commitment to the Candidate: 

Strengths 

 A letter of support by the Chief of Infectious Diseases guarantees 75% protected research 

time with clinical activities restricted to 10%. Space and K08 independent resources are 

guaranteed. 

 The environment at the Ragon Institute and Harvard School of Public Health is superb to 

pursue mechanistic studies of antibody Fc mediated effector functions in TB. The TB 

research community in Boston is outstanding. Access to all services including state of the 

art high throughput profiling, systems serology and imaging is in place. 



Weaknesses 

 None noted 



Critique 2 

Candidate: 2 

Career Development 2 

Plan/Career Goals /Plan to 

Provide Mentoring: 

Research Plan: 2 

Mentor(s), Co-Mentor(s), 1 

Consultant(s), 

Collaborator(s): 

Environment Commitment 1 
 

 

 

 

 

 

 

 

 

 

 

 

 

1 K08 AI130357-01 7 MID-B 

LU, L 

to the Candidate: 

Overall Impact: 

The candidate’s background in biology and immunology is excellent. The research experiences and 

publications are adequate to this stage of the candidate’s career. The facilities available and 

mentorships are excellent. The research plan is novel, well written and interesting. The candidate’s 

recent publication in a high impact factor journal demonstrate the significance of his research to the 

tuberculosis community. The research plan shows minor weaknesses on details such as a lack of 

definition for patients with latent disease. With adequate mentorship the candidate is on a path to 

become an independent researcher in this field. 

1. Candidate: 

Strengths 

 The candidate is an MD, PhD with a good background in biology, molecular virology, 

immunology and infectious disease. 

 The research in Saccharomyces cerevisiae DNA replication and signaling in innate immunity 

demonstrate the candidate adequate training experience for this award. The recent 

publication in Cell on the role for antibodies in tuberculosis makes the candidate highly 

qualified for this application. 

 The letters of support are excellent and enthusiastically support candidate’s potential to 

develop as an independent researcher. 

Weaknesses 

 None 

2. Career Development Plan/ Career Goals & Objectives: 

Strengths 

 The role of humoral immune response to M. tuberculosis is an area in tuberculosis research 

that has not been extensively explored, and the role of antibodies in signaling via FC domain 

has become more attractive in recent past. The investigator is highly qualified to 

successfully execute the goals of this project. 

 Humoral immunity and the role of FC domain in M. tuberculosis pathogenesis has potential 

to develop into a long term research career. 

Weaknesses 

 None 



3. Research Plan: 

Strengths 

 The candidate aims to study the humoral immunity and the role of the FC domain in M. 

tuberculosis pathogenesis. This is a novel and very stimulating new area of research in the 

tuberculosis. 
 

 

 

 

 

1 K08 AI130357-01 8 MID-B 

LU, L 

 The investigator experience in immunology and dsRNA signaling clearly indicate the ability 

to carry on this project. 

Weaknesses 

 The candidate’s application aim to study the humoral signature associated with different TB 

disease states. Preliminary results have shown differences in FC effectors and macrophage 

restriction to M. tuberculosis between active and latent disease. It is not clear how patients 

with latent disease will be identified in this application. Are these patients TST positive? 

IGRA positive? Both? Have they ever developed disease? Were they ever treated? 

4. Mentor(s), Co-Mentor(s), Consultant(s), Collaborator(s): 

Strengths 

 The candidate’s mentors are excellent with a vast experience in tuberculosis and 

immunology. 

 The mentors are fully supportive of the candidate and able to guide the candidate to develop 

as an independent researcher in the tuberculosis field. 

Weaknesses 

 None 

5. Environment and Institutional Commitment to the Candidate: 

Strengths 

 The institutions are outstanding and clearly committed to provide and facilitate the candidate 

to accomplish the research project. 

 The institution is supportive and committed to help the candidate to a career development 

which may lead to an independent scientific career. 

Weaknesses 

 None 

Critique 3 

Candidate: 1 

Career Development 1 

Plan/Career Goals /Plan to 

Provide Mentoring: 

Research Plan: 2 

Mentor(s), Co-Mentor(s), 1 

Consultant(s), 

Collaborator(s): 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1 K08 AI130357-01 9 MID-B 

LU, L 

Environment Commitment 1 

to the Candidate: 

Overall Impact: 

An exceedingly well trained Instructor in Medicine from the Massachusetts General Hospital, Harvard 

Medical School and the Ragon Institute has applied for K08 support to continue her career 

development as a physician/scientist. Her application includes three very well integrated aims that seek 

to define antigen specificity and the potential role of Fc/FcR mediated intracellular M. tuberculosis 

restriction and to identify key macrophage effector mechanisms responsible for this control. Enthusiasm 

for the application is based on the track record of the applicant, the strength and novelty of the 

preliminary data, the expertise and commitment of the mentors and the critical importance of 

developing a deeper understanding of the role of humoral immunity in the pathogenesis of 

mycobacterial infection. 

1. Candidate: 

Strengths 

 Dr. Lu is extremely well trained in both laboratory science and clinical medicine. Research 

training includes an honors thesis at Swarthmore focused on cell cycle regulation in 

Saccharomyces cerevisiae and a very productive investigation of IRF3 regulation by dsRNA 

during her MD/PhD studies at the Cleveland Clinic. 

 Her interest in tuberculosis was stimulated by a very positive experience at GHESKIO in Haiti 

during her residency at Cornell. 

 She has continued to build her research skills during her fellowship in the laboratories of Galit 

Alter and Sarah Fortune with studies of the role of humoral responses to M. tuberculosis in 

protection from disseminated mycobacterial infection. Her first manuscript in this area is in 

press in Cell. 

Weaknesses 

 No major weaknesses 

2. Career Development Plan/ Career Goals & Objectives: 

Strengths 

 Dr. Lu has outlined a very well reasoned pathway forward that will prepare her for a productive 

career as a physician scientist. 

 The project she has outlined is a logical extension of the work she has undertaken as a fellow. 

She is appropriately poised to move from describing the differences in antibody profiles from 

patients with contained (latent) vs. active M. tuberculosis infection to studies that seek to 

understand the mechanisms that might underlie effector functions of these antibodies. 

 She has already undertaken and has outlined additional formal coursework in immunology 

and biostatistics that will complement her experiential training extremely well. 

Weaknesses 
 

 

 

 

 

1 K08 AI130357-01 10 MID-B 

LU, L 

 It will be important for the applicant to maintain engagement with the clinical community 

engaged in care for patients with M. tuberculosis infection during the five years of this K08. 

She might benefit from scientific or clinical engagement with GHESKIO, PIH, K-RITH or any 

number of Harvard’s multiple clinical tuberculosis programs. 

3. Research Plan: 

Strengths 

 The research plan builds on the work undertaken during her fellowship and takes full 

advantage of the deep bench of researchers focused on M. tuberculosis in the Boston area as 

well as the cutting edge immunologic expertise at the Ragon Institute. 

 The proposed research focuses on an area of mycobacterial immunity that has been 

traditionally neglected compared to studies of innate and cellular immunity. 

 If successful, the research might provide useful insights into the pathogenesis of 

mycobacterial infection as well as to lead toward the discovery of biomarkers that could be 

useful for diagnosis and prognosis. 

 Should humoral immunity be more central to the pathobiology of mycobacterial infection than 

has traditionally been posited, the work could lead toward novel approaches to mycobacterial 

vaccine development. 

 The research plan is logically organized and the specific aims are well integrated. 

 The focus on FcR mediated antibody (as opposed to neutralization-based) antibody activity is 

novel and highly testable. 

Weaknesses 

 Although it is highly innovative to focus this work on humoral immune responses to 

mycobacterial infection, one potential wrinkle that should be considered (in view of the FcR 

emphasis of the proposal) is whether changes in effector cell characteristics in patients with 

cellular immunodeficiency could undermine the effectiveness of humoral effectors. For 

example, FcR mediated mechanisms might be very important in defense from M. tbc. Infection 

in patients with functional mononuclear cell repertoires but non-functional in environments in 

which HIV has distorted effector populations. If a role for FcR-Ab mediated protection is noted, 

is there a plan to see whether these functions are affected in the cells obtained from patients 

with advanced HIV infection? 

4. Mentor(s), Co-Mentor(s), Consultant(s), Collaborator(s): 

Strengths 

 Drs. Alter and Fortune are outstanding mentors for this early career scientist. Their 

complementary expertise in immunology and in mycobacterial pathogenesis will provide 

mentorship in both aspects of Dr. Lu’s highly innovative project. 

 Her advisory committee is likewise very well constituted with the involvement of Drs. Batista, 

Iwasaki, Nimmerjahn and Rubin. 

 Research samples from Dr. Restrepo’s very well characterized cohort will also be extremely 

valuable to Dr. Lu. 

Weaknesses 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1 K08 AI130357-01 11 MID-B 

LU, L 

 None 

5. Environment and Institutional Commitment to the Candidate: 

Strengths 

 The Ragon Institute is a superb location for training in all aspects of immunology and, as 

noted above, the Harvard milieu for mycobacterial research is outstanding. 

 The applicant’s letter of support from her Division Head is unequivocal. She already has a 

faculty appointment and will be asked to devote no more than 10% of her time to clinical 

activities. 

Weaknesses 

 None 

THE FOLLOWING RESUME SECTIONS WERE PREPARED BY THE SCIENTIFIC REVIEW 

OFFICER TO SUMMARIZE THE OUTCOME OF DISCUSSIONS OF THE REVIEW COMMITTEE ON 

THE FOLLOWING ISSUES: 

PROTECTION OF HUMAN SUBJECTS (Resume): Code: 30 ACCEPTABLE

The study enrolls individuals with latent or active TB who are willing and able to give informed consent 

and are adult males and females aged 18-75. Study sites take place in University of Texas Health 

Science Center at Houston-School of Public Health-Brownsville Regional Campus in association with 

Hidalgo County Health Department and Cameron County Health Department and or MGH Infectious 

disease clinical sites as noted above. 

Projects to be undertaken with support of this training grant, which involve human subjects, must 

conform to the NIH policies on the protection of human subjects. Guidance can be found in PHS398 

application materials and the NIH Office of Extramural Research web site 

http://grants.nih.gov/grants/policy/hs/index.htm. 

DATA AND SAFETY MONITORING PLAN: ACCEPTABLE 

INCLUSION OF WOMEN PLAN (Resume): Code: G1A ACCEPTABLE 

Eligible adult males and females from all ethnic backgrounds are included in the cohorts utilized in this 

study. 

Projects to be undertaken with support from this training grant, which involve clinical research studies, 

must conform to the NIH policies on the inclusion of women in study populations. See 

http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. Details of such 

studies, including a description of the population and rationale for inclusion/exclusion, must be provided 

to the NIH program administrator of this training grant prior to undertaking the studies. 

INCLUSION OF MINORITIES PLAN (Resume): Code: M1A ACCEPTABLE 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1 K08 AI130357-01 12 MID-B 

LU, L 

Eligible adult males and females from all ethnic backgrounds are included in the cohorts utilized in this 

study. 

Projects to be undertaken with support from this training grant, which involve clinical research studies, 

must conform to the NIH policies on the inclusion of minorities in study populations. 

See http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. Details of 

such studies, including a description of the population and rationale for inclusion/exclusion, must be 

provided to the NIH program administrator of this training grant prior to undertaking the studies. 

Comments or Concerns: No concerns. Most or all biological specimens will come from 

established specimen repositories. Furthermore, since M. tuberculosis disproportionately affects 

members of traditionally underrepresented groups, it would be expected that samples from this 

population will be well represented. 

INCLUSION OF CHILDREN PLAN (Resume): Code: C3A ACCEPTABLE 

No children will be included. 

Projects to be undertaken with support from this training grant, which involve clinical research studies, 

must conform to the NIH policies on the inclusion of children in study populations. See 

http://grants.nih.gov/grants/funding/children/children.htm. Details of such studies, including a 

description of the population and rationale for inclusion/exclusion, must be provided to the NIH program 

administrator of this training grant prior to undertaking the studies. 

VERTEBRATE ANIMALS (Resume): Code: 10 NOT APPLICABLE

No vertebrate animals will be used in this application. 

BIOHAZARD COMMENT: ACCEPTABLE 

Biohazards, if present, are named and appropriate responses and handling procedures given. 

Comments or Concerns: The applicant has access BSL 3 space both at the Ragon Institute and at the 

Harvard School of Public Health. Procedures for working with mycobacteria are in place and there are 

no concerns. 

TRAINING IN THE RESPONSIBLE CONDUCT OF RESEARCH: ACCEPTABLE 

Format: 

Subject Matter: 

Faculty Participation: 

Duration: 

Frequency: 

Comments: 

Format: Experiential, didactic and seminar based 

Subject Matter: research ethics, regulatory requirements, subject privacy and other key areas 

of instruction. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1 K08 AI130357-01 13 MID-B 

LU, L 

Faculty Participation (Not applicable for mid-career (K24) and senior-candidate awards): full 

participation of mentorship committee 

Duration: Initial coursework involving 16 hours of face time. 

Frequency: Biannual discussions with her advisory committee about 

FOREIGN INSTITUTION: NOT APPLICABLE 

SELECT AGENTS: NOT APPLICABLE 

RESOURCE SHARING PLANS: ACCEPTABLE 

Data Sharing Plan Comments (if >$500,000/year): 

Sharing Model Organisms Comments: 

Genomic Data Sharing (GDS) Comments: 

Consistent with NIH and institutional guidelines 

AUTHENTICATION OF KEY BIOLOGICAL AND/OR CHEMICAL RESOURCES: ACCEPTABLE 

BUDGET AND PERIOD OF SUPPORT: The budget was recommended as requested. 

Footnotes for 1 K08 AI130357-01; PI Name: Lu, Lenette 

NIH has modified its policy regarding the receipt of resubmissions (amended applications). 

See Guide Notice NOT-OD-14-074 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD14-074.html. The impact/priority score is calculated after discussion of an application by 

averaging the overall scores (1-9) given by all voting reviewers on the committee and 

multiplying by 10. The criterion scores are submitted prior to the meeting by the individual 

reviewers assigned to an application, and are not discussed specifically at the review meeting 

or calculated into the overall impact score. Some applications also receive a percentile 

ranking. For details on the review process, see 

http://grants.nih.gov/grants/peer_review_process.htm#scoring.