SUMMARY STATEMENT

PROGRAM CONTACT: ( Privileged Communication ) Release Date:

Tonu Wali Revised Date:

240-627-3389

twali@mail.nih.gov

12/02/2016

Principal Investigator 

TRAN, TUAN MANH

Application Number: 1 K08 AI125682-01A1

Applicant Organization: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS

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: M44

Requested Start: 04/01/2017

Project Title: Defining clinical and sterile immunity to Plasmodium falciparum infection using 

systems biology approaches

SRG Action: Impact Score:

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

Human Subjects: E4-Human subjects involved - Exemption #4designated

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

Clinical Research - not NIH-defined Phase III Trial

Project

Year

Direct Costs

Requested

Estimated

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.

Time has passed since the application was reviewed. This sample may 

not reflect the latest format for summary statements. NIAID posts new 

samples periodically: https://www.niaid.nih.gov/grants-contracts/sampleapplications

The text from the application is copyrighted. You may use it only for 

nonprofit educational purposes provided the document remains unchanged 

and the PI, the grantee organization, and NIAID are credited.

Contact information. If you have any questions, email the NIAID Office of 

Knowledge and Educational Resources at deaweb@niaid.nih.gov. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1 K08 AI125682-01A1 2 MID-B
 

TRAN, T 

1K08AI125682-01A1 Tran, T 

BIOHAZARD COMMENT 

FOREIGN INSTITUTION 

RESUME AND SUMMARY OF DISCUSSION: This exceptional resubmission application for a 

Mentored Clinical Scientist Research Career Development Award (K08) entitled “Defining clinical and 

sterile immunity to Plasmodium falciparum infection using systems biology approaches” was submitted 

by Tuan Tran, MD, PhD of Indiana University. 

This K08 award will provide the candidate, Dr. Tuan Manh Tran, with training and resources to further 

develop his career expertise in the field of malaria-systems biology. The main goal of this application is 

to use systems biology methods to elucidate correlates and mechanisms of both clinical and sterile 

immunity to P. falciparum infection. A well-characterized cohort of Malian children living in an area of 

intense, seasonal malaria transmission will be utilized. The work will be performed under two specific 

aims. Aim 1: Identify immune parameters predictive of clinical immunity to Pf infection and sterile 

immunity to Pf infection. Aim 2: Compare cellular, molecular, and Pf-specific IgG reactivity profiles in 

the blood of children with clinical vs sterile immunity and relate these profiles and immune outcomes to 

the in vitro parasite-inhibitory activity of their plasma. 

Among strengths is a significant but challenging project to examine the correlates and mechanisms of 

clinical and sterile immunity to Plasmodium falciparum (Pf) infection. Currently an assistant professor in 

the Indiana University School of Medicine, this highly qualified candidate has received both MD and 

PhD degrees and training from an internship and residency at the Johns Hopkins Hospital and a 

research fellowship in NIAID. In addition to his immunology and infectious disease experience, the 

candidate has computational and systems biology skills. This resubmission is markedly improved with 

minor issues remaining in the research plan mainly because of the nature of the project. The mentoring 

team is well qualified and patient samples from Mali provide a well-characterized source of clinical data 

for the applicant’s systems biology approaches. 

Among weaknesses primarily in the research plan, are the questionable rigor and statistical power of 

the project, the host genetic background issue, and the observation that this project may not result in a 

substantial publication output. Despite these weaknesses, the panel had great enthusiasm for the 

candidate’s potential impact in clinical research. Based upon the evaluation of scientific and technical 

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

DESCRIPTION (provided by applicant): 

Project Summary/Abstract Malaria afflicts ~198 million people yearly, with 438,000 malaria deaths due 

to Plasmodium falciparum, underscoring the need for a highly effective malaria vaccine. The first 

licensed malaria vaccine, RTS,S, may provide much-needed reductions in morbidity and mortality, but 

its modest efficacy in reducing clinical malaria in the target population of African infants leaves ample 

margin for improvement. A better understanding of immunity to P. falciparum in naturally exposed 

populations can inform efforts to improve malaria vaccine design. To date, there are no reliable 

correlates of protection from either symptomatic P. falciparum infection (clinical immunity) or 

parasitemia (sterile immunity). Systems biology utilizes computational modeling of large- scale data 

sets to elucidate complex biological networks and has the potential to reveal novel predictors and 

mechanisms of malaria protection when applied to well-designed clinical cohort studies. In this project, 

the candidate proposes to assess immune predictors of natural protection from P. falciparum infection 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1 K08 AI125682-01A1 3 MID-B
 

TRAN, T 

using systems biology approaches. By analyzing clinical data and blood specimens collected from a 

well-characterized, prospective cohort of Malian children who differ in their degree of immunity to P. 

falciparum infection, the candidate will address two main research aims: 1) determine immune 

parameters predictive of protection from symptomatic infection (clinical immunity) and protection from 

P. falciparum infection (sterile immunity) and 2) relate these immune parameters and outcomes to the 

ability of plasma obtained from these children to inhibit parasite invasion into liver and red blood cells in 

vitro. The practical implications of this work include identifying novel immune predictors and 

mechanisms of protection from P. falciparum infection and disease within the vaccine target population 

that could provide rational benchmarks for candidate malaria vaccines. The candidate is firmly 

committed to a career in translational malaria research and systems biology and is strongly supported 

in his career and research goals by his mentors and his division at the Indiana University School of 

Medicine. He currently holds a position as an Assistant Professor of Medicine with 80% protected time 

for research, independent laboratory and office space, and funding for equipment. The current proposal 

includes a comprehensive mentorship and didactic plan to advance the candidate's skills and 

knowledge in biostatistics and computational biology required for developing expertise in systems 

biology. Under the guidance of his primary mentor, Dr. Chandy John, and his co-mentors, Dr. Wanzhu 

Tu, Dr. Lang Li, and Dr. Peter Crompton, he will advance his bioinformatics skills and learn predictive 

modeling methodologies that will be directly applied to this proposal. Completion of this comprehensive 

training plan will provide the candidate with the skills and experience necessary to become a successful 

independent investigator specializing in computational systems biology with a focus on host immunity to 

Plasmodium infection. 

PUBLIC HEALTH RELEVANCE 

Project Narrative Each year malaria afflicts ~200 million people and causes over 430,000 deaths, 

primarily among African infants. Although a first-generation malaria vaccine is now available, it is only 

modestly effective in the target population of African infants; thus, a better understanding of natural 

immunity to Plasmodium falciparum, the deadliest of malaria parasites, in young African children can 

inform efforts to develop the next generation of malaria vaccines. Using samples collected from young 

Malian children before and during natural P. falciparum infections, this study aims to identify predictors 

and mechanisms of malaria immunity that aid the development of future malaria vaccines. 

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 1 

Plan/Career Goals /Plan to 

Provide Mentoring: 

Research Plan: 3 

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

Consultant(s), 

Collaborator(s): 

Environment Commitment 1 

to the Candidate: 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1 K08 AI125682-01A1 4	 MID-B
 

TRAN, T 

Overall Impact: 

The candidate is a talented researcher with outstanding training in infectious diseases (esp. malaria), 

immunology, and applied bioinformatics. This project aims to use systems biology approaches to 

address an important and challenging question, i.e., what are the correlates and mechanisms of both 

clinical and sterile immunity to Plasmodium falciparum (Pf) infection. From a well-collected cohort, data 

from various arrays (e.g., transcriptomics, flow cytometry data, Pf genetic differences) will be generated 

and used. Statistical modeling and analysis are proposed to utilize these data. This is a resubmission. 

The candidate has improved this application by appropriately addressing most comments from the 

previous submission. However, the host genetic background issue, as commented previously, could be 

be better addressed. Other research design methods could also be improved with more convincing 

details. To ensure future R01 submission, the candidate is also advised to systematically analyze 

detailed immune pathways and identify potential novel hypotheses. 

1. Candidate: 

Strengths 

	 The candidate is currently an assistant professor in the Indiana University School of 

Medicine (IUSM), Indianapolis. He got his MD, PhD in Immunology and Molecular 

Pathogenesis, Internship and residency in the John Hopkins Hospital, and fellowship in 

NIAID. 

	 The candidate learned computational and systems biology methods during his fellowship 

training in NIAID. 

	 He has published over 20 peer-reviewed articles, with 12 focusing on naturally acquired 

immune responses to malaria in endemic populations. His malaria research started from the 

Graduate School. 

Weaknesses 

	 No significant weaknesses were noted. 

2. Career Development Plan/ Career Goals & Objectives: 

Strengths 

	 The candidate’s long term goal is to become an expert in the field of systems biology of 

malaria. He is interested in studying host immune responses to Plasmodium infection in the 

endemic setting using systems-based analysis. 

	 His short term K proposal goal is to determine the immune parameters for predicting the 

outcomes of a child protected from malaria symptoms or parasitemia. 

	 The candidate’s long term and short term goals fit very well with the candidate’s 

interdisciplinary trainings in infectious diseases, immunology, field research, and 

bioinformatics. 

Weaknesses 

	 The candidate will need more knowledge and skills in biostatistics and mathematical 

modeling. This is an objective from this K grant. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1 K08 AI125682-01A1 5	 MID-B
 

TRAN, T 

3. Research Plan: 

Strengths 

	 Systems biology approaches are proposed. Such approaches are appropriate to elucidate 

correlates and mechanisms of both clinical and sterile immunity to Pf infection. 

	 A well-characterized, prospective cohort of Malian children living in an area of intense, 

seasonal malaria transmission will be used. The cohort includes longitudinally collected 

biospecimens (plasma/whole-blood RNA/DBS/PBMCs) linked to >3 years of prospective 

clinical, parasitological, and epidemiological data. 

	 In Aim 1, data from different assays, such as whole-blood transcriptomics, multi-parameter 

flow cytometry, multiplex cytokine analysis, and pathogen genetic differences will be used. 

These provide a broad range of data sets for predicting immune correlates of clinical or 

sterile protection from Pf infection. 

	 Different Multi-parameter statistical modeling and machine learning methods will be used for 

predicting clinical and sterile immunity. 

	 As suggested by the review comments from the first submission, this application has 

combined the original aims into a single Aim 1 and introduced a revised Aim 2 that 

comparatively analyzes clinical and sterile immunity and integrates data from functional 

assays. 

Weaknesses 

	 A major comment from previous submission is the lack of genetic analysis of human hosts. 

The current proposal proposes to perform ABO blood group typing, and genotype for most 

common α+-thalassemia, and G6PD deficiency variants of erythrocytes (3.2.2b). It partially 

addresses the previous comment. The previous comment also suggested possible new 

layers of “omic” data for host genetic background to determine significant molecular 

signatures to clinical and sterile immunity. Such host genetic background omic data is not 

proposed or discussed in the current proposal. Considering that a huge amount of data have 

already been included, this is considered a relatively minor issue for this application; 

however, an omics data analysis of host genetic background to identify susceptible genetic 

variability may be an important task to perform in the future. 

	 Aim 1 statistical modeling for predicting clinical or sterile immunity has its weaknesses. In 

Aim 1, machine learning approaches are used to determine which variables (features) from 

demographic (i.e. age, gender), epidemiological, erythrocyte variant, parasitological, 

transcriptomic, FACS, multiplex cytokine, and Pf-specific IgG data could best predict clinical 

or sterile immunity. This is not a trivial task. Although it is possible to find individual features 

able to predict the outcomes, it is very likely that in this complex system, many features are 

required together in a combinatory set to predict the outcomes. However, it can be very 

tricky to find what combinations of features to use and the sizes of features in such 

combinations. Also, instead of looking for individual features, we may often want to examine 

the interaction pathways (another layer) among these features that may become better 

predictors of clinical or sterile immunity. These aspects have not been discussed. 

	 Other than predicting clinical or sterile immunity, an important part of the study would be to 

identify the immune pathway mechanisms. Predictors (as emphasized in the current 

proposal) may predict well; however, they may not be able to well illustrate the mechanisms 

or it may be hard to explain the functions of these predictors. The identification of key 

immune factors and related pathways for future hypothesis generation and verification 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1 K08 AI125682-01A1 6	 MID-B
 

TRAN, T
 

wound be important for extended research. Such aspect is not emphasized in the current 

proposal. 

	 The above weaknesses are considered addressable. 

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

Strengths 

	 The candidate has assembled a strong mentoring team to support various aspects of 

training. 

	 Dr. Chandy C. John, a professor of pediatrics as well as Microbiology and Immunology at 

IUSM, will act as the primary mentor. He has received continuous NIH funding since 1999 to 

study malaria immuno-epidemiology and malaria pathogenesis in Africa. 

	 Dr. Wanzhu Tu, a professor of biostatistics at IUSM, will serve as a co-mentor. Dr. Tu has 

strong background in using statistical methods to model biological processes and 

understand diseases. 

	 Dr. Lang Li, a professor and Director of the Center for Computational Biology and 

Bioinformatics at IUSM, will serve as a co-mentor. He will provide the guidance and 

resources to properly execute predictive modeling algorithms. 

	 Dr. Peter D. Crompton, Chief of the Malaria Infection Biology and Immunity Unit at NIAID will 

also serve as a co-mentor. Dr. Crompton was the candidate’s primary research mentor 

during his fellowship at NIAID. Dr. Crompton will provide expertise in human immunity to 

Plasmodium infection. 

Weaknesses 

	 No significant weaknesses were noted. 

5. Environment and Institutional Commitment to the Candidate: 

Strengths 

	 The environment for conducting the proposed research is excellent. 

Weaknesses 

	 Not observed. 

Critique 2 

Candidate: 1
 

Career Development 2
 

Plan/Career Goals /Plan to
 

Provide Mentoring:
 

Research Plan: 4
 

Mentor(s), Co-Mentor(s), 3
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1 K08 AI125682-01A1 7	 MID-B
 

TRAN, T 

Consultant(s), 

Collaborator(s):
 

Environment Commitment 2
 

to the Candidate:
 

Overall Impact: 

This resubmission of an application for a Mentored Clinical Scientist Research Career Development 

Award (K08) provides further evidence of an outstanding candidate, supported by a team of wellqualified mentors and collaborators. A strength of the application is its documentation of a candidate 

suitably-prepared for this career development step and the training program and mentorship in place for 

him to achieve that. The research plan itself almost assures that the candidate will gain valued 

experience with theory, new methods, and computational approaches that will advance his stated 

research goals. What remains insufficiently addressed in the resubmission is the concern that the 

research project in the end will largely be inconclusive, mainly because it was under-powered for the 

wide-ranging scope. This may leave the candidate in a vulnerable position near the end of the CDA, 

and the inattention to this possibility has to reflect on the quality of the mentorship. 

1. Candidate: 

Strengths 

	 The candidate, Tuan Tran, MD, PhD, an Assistant Professor of Medicine at Indiana 

University since 2015, has had excellent training and experience in clinical medicine and 

laboratory research at such institutions as Emory University, Johns Hopkins, and the 

intramural program of the National Institutes of Health. 

	 For a young physician-scientist who has much of his time devoted to full-time clinical 

activities, Dr. Tran's publication record is excellent. 

	 The background and present skill-set of the candidate prepares him well for moving beyond 

the domains of clinical research and laboratory research to a more integrative discipline. Dr. 

Tran is an outstanding prospect for a successful career in clinical and translational research. 

Weaknesses 

	 A minor detracting point is the needless use of the third person singular instead of first 

person by the candidate in the abstract and the frequent use of “we” elsewhere. It gives the 

impression of either a reluctance of the candidate to assume ownership or some wellmeaning but bad advice. 

2. Career Development Plan/ Career Goals & Objectives: 

Strengths 

	 The K08 mechanism is highly appropriate for this candidate at this stage in his career. 

	 The candidate and mentors have identified suitable didactic and tutorial experiences for the 

goals of the career development and 

Weaknesses 

	 This may be "systems" biology in the sense of utilizing data sets of different types of 

information (e.g. the immunlogy "system"), but it is not really "systems biology" as the term 

is most commonly used currently, i.e. "...the focus on the dynamics of the studied systems is 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1 K08 AI125682-01A1 8	 MID-B
 

TRAN, T
 

the main conceptual difference between systems biology and bioinformatics" (Wikipedia 

entry). The research plan seems to be more devoted to identifying informative predictors 

across different data sets than characterizing the interactions themselves. That's fine, as 

discussed below, but it may be doing the candidate a disservice to promote a description 

that others (including potential recruiters) would assign another name to. 

	 While the training aspects fit well with the candidate’s career development goals, but it is 

harder to see how the research project could realistically evolve to a competitive R01 

application. This was a concern that a previous reviewer had brought up. 

3. Research Plan: 

Strengths 

	 The study's overall goal to identify transcriptomics, serum biomarkers, antigen reactivity 

profiles, and other molecular signatures that predict and distinguish between clinical 

immunity and apparent sterile immunity is meritorious. 

	 The candidate clearly has his research tools in place to carry out these types of studies, 

either through his own lab or others in Indiana or through collaborations, such as with Dr. 

Felgner in California. 

	 The research plan without doubt will provide the candidate with “priceless” research 

experiences that will serve him well for design and implementation of studies in the future. 

Weaknesses 

	 A previous reviewer wrote that “weaknesses that reduce enthusiasm are concerns regarding 

the lack of genetic analysis of human hosts.” The reviewer had in mind specifically certain 

hemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency. New research 

plan incorporates these as characters, but there was little consideration of the genetics of 

the host or of the target population beyond that limited set of genotypes. Although some 

genome scan or candidate gene studies have proven to be inconclusive or unreplicable with 

respect to malaria susceptibility and disease outcome, there is a growing literature on 

candidate variants associated with large or small effect sizes as well as biological 

plausibility. Stratification on the basis of this or that allele would, of course, add to the 

challenge of attaining sufficient sample sizes. But if the goal is a project that extends more 

than a couple of years into the future--and to be funded, greater incorporation of the host 

genetics parameter into the model would seem to be an essential. 

	 Although it seems there has been an increase in the sample sizes from the first application, 

the provisional sample sizes of less than 100 for each group (Table 3) still seem to pose a 

substantial risk of ending up with an under-powered study (even if there is the disclaimner of 

it being “exploratory”). This is especially a concern given (a) the huge number of “tests” that 

will be performed by transcriptomics, protein arrays, and biomarkers, (b) the heterogeneity 

of the study population in age (7 to 18 years), sex, and ethnicity, and (c) the not-discounted 

possibility of assignment of some of the subjects to the wrong group. There was no mention 

of the nutritional state of the children as a consideration or anything about the population 

structure in the study. Importantly, what about other infections the children may have at the 

time of the blood sample? 

	 The machine learning approach in addition to standard regression models is reasonable, but 

how will the “winner” output algorithms of the machine learning be interpreted? Obviously 

they would need to be tested with an independent dataset, but the algorithm may still be 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1 K08 AI125682-01A1 9	 MID-B
 

TRAN, T
 

effectively incomprehensible. In other words, it works great as a predictor, but it’s not clear 

to us humans why it works. 

	 There was insufficient consideration of some possible pitfalls. The most worrying one is that, 

for one reason or another, the candidate will not have access to that study population in 

Mali. Is there a backup study site? On pg. 110 sites in Uganda and Kenya are mentioned, 

but these are not explicitly referenced as alternative study sites for this particular study. 

Another, more minor concern is whether for RNA-seq 25 million paired-end reads of globlinand rRNA-depleted cDNAs can be achieved from a single fingerstick sample. 

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

Strengths 

	 The primary mentor, Dr. Chandy John (Indiana University), and co-mentors Wanzhu Tu 

(Indiana University), Lang Li (Indiana University), and Peter Crompton (NIH) were wellqualified to serve in these roles. 

	 The collaborators Sangeeta Bhatia (MIT), Philip Felgner (UC Irvine), Scott Michaels 

(Indiana University), and Kara Wools-Kaloustian (Indiana University) provide complementary 

expertise and resources to the research project. 

Weaknesses 

	 The short-comings of the research plan of this resubmission raises a question about the 

quality of the mentorship to date. 

5. Environment and Institutional Commitment to the Candidate: 

Strengths 

 The environments of Indiana University as well as the collaborating institutions for carrying 

Weaknesses 

	 The expertise and resources of the institutions are particularly suited for a bioinformatics, 

computation science, and biostatistics oriented training program and research project, but 

not demonstrably "systems biology", as it is usually thought of. This may not be important for 

what the candidate proposes to actually do, but it is another example of how the application 

title could be misleading. 

Critique 3 

Candidate: 1
 

Career Development 1
 

Plan/Career Goals /Plan to
 

Provide Mentoring:
 

Research Plan: 3
 

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

Consultant(s),
 

Collaborator(s):
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1 K08 AI125682-01A1 10	 MID-B
 

TRAN, T 

Environment Commitment 1
 

to the Candidate:
 

Overall Impact: 

This resubmission K08 from a highly productive Assistant Professor at Indiana University proposes to 

study the mechanisms of immunity to malaria in Mali using a systems biology approach. The 

resubmitted proposal has done much to strengthen an already solid proposal. The candidate and 

institutional commitment is outstanding, and the mentorship team is likewise exceptional. There exist 

minor concerns about the research strategy, but given the many strengths of this application, there is 

high enthusiasm that it will lead to substantial overall impact. 

1. Candidate: 

Strengths 

	 Academic productivity (with >20 manuscripts already published, only one year after 

completing fellowship) is exceptional. 

	 All letters recommend the applicant with utmost enthusiasm. 

	 Easy to see how this applicant’s unique skill set in systems biology and application to a 

disease of great global importance will lead to a productive and potentially transformative 

career. 

Weaknesses 

	 None noted 

2. Career Development Plan/ Career Goals & Objectives: 

Strengths 

	 Training plan is well thought-out and includes a nice blend of mentored training, didactic 

activities, and hands-on experience with skills such as writing. 

	 Need for further training is well articulated, and it is clear how that additional training will 

further the applicant’s research career. 

	 Very feasible timeline ending in submission of R01 proposal in Year 4-5. 

Weaknesses 

	 None noted 

3. Research Plan: 

Strengths 

	 Appropriate methodology outlined, with high likelihood of success in answering important 

questions. 

	 Completing these analyses will provide the applicant important experience in the methods 

he proposes to master. 

	 Clear path identified to how this research plan will result in continued academic productivity 

on the part of the applicant. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1 K08 AI125682-01A1 11	 MID-B
 

TRAN, T 

	 Revised plan (with a new Aim 2) is well justified and, if successful, will result in major 

advances in knowledge. 

Weaknesses 

	 Sample size/power remains an issue, with a relatively small number of clinical isolates 

available (especially of infants who are clinically immune) – though approaches to address 

this limitation seem appropriate. 

	 Revised proposal now includes a tremendous body of work, with many combinatorial 

analyses – may be difficult for the applicant to complete all of this within the course of his K 

(though even a valiant attempt to do so would arguably be worthwhile). 

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

Strengths 

	 Exceptionally strong mentorship team, with the complementary expertise needed to help the 

applicant succeed. 

	 Applicant has a good history of collaboration with Dr. Crompton and an emerging 

relationship with other mentors on his team. 

	 Dr. John is a distinguished mentor and clearly dedicated to the applicant’s career 

development. 

Weaknesses 

	 None noted 

5. Environment and Institutional Commitment to the Candidate: 

Strengths 

	 Strong combination of personnel and facilities that are necessary to facilitate the applicant’s 

eventual transition to independence 

	 Patient samples from Mali provide a well-characterized source of clinical data, as necessary 

for the applicant’s systems biology approaches 

	 Institution is very highly committed to this applicant, having already offered a tenure-track 

faculty position. The applicant is in prime position to benefit from a K08 award. 

Weaknesses 

	 None noted 

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: E4 ACCEPTABLE 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1 K08 AI125682-01A1 12 MID-B
 

TRAN, T 

This application qualifies as Exempt Human Subjects Research. The current proposal will only utilize 

existing, “in-the-freezer” human biological specimens and existing clinical data from an ongoing cohort 

study on naturally acquired malaria immunity in Kalifabougou, Mali. 

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. 

INCLUSION OF WOMEN PLAN (Resume):

This proposal qualifies as Exempt Human Subjects Research. The current proposal will only utilize 

existing, “in-the-freezer” human biological specimens and existing clinical data from an ongoing cohort 

study on naturally acquired malaria immunity in Kalifabougou, Mali. 

INCLUSION OF MINORITIES PLAN (Resume):

This proposal qualifies as Exempt Human Subjects Research. The current proposal will only utilize 

existing, “in-the-freezer” human biological specimens and existing clinical data from an ongoing cohort 

study on naturally acquired malaria immunity in Kalifabougou, Mali. 

INCLUSION OF CHILDREN PLAN (Resume):

This proposal qualifies as Exempt Human Subjects Research. The current proposal will only utilize 

existing, “in-the-freezer” human biological specimens and existing clinical data from an ongoing cohort 

study on naturally acquired malaria immunity in Kalifabougou, Mali. 

VERTEBRATE ANIMALS (Resume): Code: 10 NOT APPLICABLE

No vertebrate animals will be used in this application. 

BIOHAZARD COMMENT: UNACCEPTABLE 

No biohazards were addressed. 

RESUBMISSION: 

Comments:
 

The candidate has appropriately addressed most comments from the previous submission. Overall, this
 

is a much improved application. However, the host genetic background issue could be better addressed
 

or discussed. The statistical modeling methods for the immune prediction could also be improved.
 

Comments: The original application was judged as “outstanding” with the greatest enthusiasm reserved
 

for the candidate himself, his accomplishments to date, and his promise. Minor weaknesses were
 

identified in the training and career development aspects. Most of the more substantive criticisms were
 

about the research plan, with four different reviewers identifying weaknesses, some of which were the
 

same in more than one review (such as a call for combining of Aims 1 and 2), but many that were
 

unique to each reviewer. The Introduction summarizes the modifications, including combining of the
 

original Aims 1 and 2 and adding a new Aim 2. Some of the remaining criticisms were satisfactorily
 

addressed by modifications in the research design, but to my eye many were not. These are discussed
 

in the relevant sections above. But a particularly cogent comment by one reviewer remains a concern
 

for me as well: “It seems a shame to take such a highly productive junior investigator and place him into
 

a situation where he is not expected to generate any research manuscripts for two years – and then,
 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1 K08 AI125682-01A1 13 MID-B
 

TRAN, T 

the manuscripts proposed could end up being relatively low impact [journal] due to concerns over 

sample size and repetition of similar analyses in the same epidemiological cohort.” 

Comments: The applicant has done a very good job of responding to the initial concerns raised about 

the scope of the research strategy, ability to maintain academic productivity, and appropriateness of the 

methods. 

TRAINING IN THE RESPONSIBLE CONDUCT OF RESEARCH: ACCEPTABLE
 

Format:
 

Subject Matter:
 

Faculty Participation:
 

Duration:
 

Frequency:
 

Training in the Responsible Conduct of Research: ACCEPTABLE 

Comments: 

Format: online and classroom 

Subject Matter: conflicts of interest, misconduct, authorship, ethics, science and society 

Faculty Participation: faculty at Indiana University 

Duration: 22.5 contact hours 

Frequency: 

FOREIGN INSTITUTION: JUSTIFIED 

Comments: 

Dr. Boubacar Traore from [Malaria Research Training Center (MRTC), University of Sciences, 

Techniques, and Technology of Bamako (USTTB), Malian International Center for Excellence in 

Research, Bamako, Mali] will be a collaborator. Dr. Traore and the candidate’s co-mentor Dr. Peter 

Crompton at NIAID have allowed the candidate access to human biological samples and clinical data 

from the Kalifabougou cohort for the current proposal. 

I 

SELECT AGENTS: NOT APPLICABLE 

RESOURCE SHARING PLANS: NOT APPLICABLE 

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

Sharing Model Organisms Comments: 

Genomic Data Sharing (GDS) Comments: 

AUTHENTICATION OF KEY BIOLOGICAL AND/OR CHEMICAL RESOURCES: ACCEPTABLE, 

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

 

 

 

 

 

 

 

 

 

1 K08 AI125682-01A1 14 MID-B
 

TRAN, T 

Footnotes for 1 K08 AI125682-01A1; PI Name: Tran, Tuan Manh 

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. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

MEETING ROSTER
 

Microbiology and Infectious Diseases B Subcommittee
 

Microbiology, Infectious Diseases and AIDS Initial Review Group
 

NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
 

MID-B November 2016
 

MID-B
 

11/04/2016 - 11/07/2016
 

CHAIRPERSON(S) 

DENISON, MARK R., MD 

PROFESSOR OF PEDIATRICS 

DEPARTMENT OF PEDIATRICS 

VANDERBILT UNIVERSITY MEDICAL CENTER 

NASHVILLE, TN 37232 

ACTING CHAIR 

LUKEHART, SHEILA A., PHD 

PROFESSOR 

DEPARTMENT OF MEDICINE 

HARBORVIEW MEDICAL CENTER 

UNIVERSITY OF WASHINGTON 

SEATTLE, WA 98104 

MEMBERS 

BARBOUR, ALAN G., MD 

PROFESSOR 

DEPARTMENT OF MICROBIOLOGY AND MOLECULAR 

GENETICS 

SCHOOL OF MEDICINE 

UNIVERSITY OF CALIFORNIA, IRVINE 

IRVINE, CA 92697 

BERGMANN, CORNELIA, PHD 

PROFESSOR 

DEPARTMENT OF NEUROSCIENCES 

LERNER RESEARCH INSTITUTE 

THE CLEVELAND CLINIC FOUNDATION 

CLEVELAND, OH 44195 

COLANGELI, ROBERTO, PHD * 

ASSISTANT PROFESSOR 

DEPARTMENT OF MEDICINE 

RUTGERS NEW JERSEY MEDICAL SCHOOL 

MEDICAL SCIENCE BUILDING (MSB) 

NEWARK , NJ 07101 

DIRITA, VICTOR J., PHD 

PROFESSOR 

RUDOLPH HUGH ENDOWED CHAIR IN MICROBIAL 

PATHOGENESIS 

CHAIR, DEPT. OF MICROBIOLOGY & MOLECULAR GENETICS 

MICHIGAN STATE UNIVERSITY 

EAST LANSING, MI 48824 

DOWDY, DAVID WESLEY, PHD, MD * 

ASSISTANT PROFESSOR 

DEPARTMENT OF EPIDEMIOLOGY 

BLOOMBERG SCHOOL OF PUBLIC HEALTH 

JOHNS HOPKINS UNIVERSITY 

BALTIMORE, MD 21205 

ENGEL, JOANNE N., MD, PHD 

PROFESSOR OF MEDICINE 

MEDICINE, MICROBIOLOGY AND IMMUNOLOGY 

UNIVERSITY OF CALIFORNIA, SAN FRANCISCO 

SAN FRANCISCO, CA 94143 

FOWLER, VANCE G. JR, MD, MHS 

PROFESSOR OF MEDICINE 

DIVISION OF INFECTIOUS DISEASES 

DEPARTMENT OF INTERNAL MEDICINE 

DUKE UNIVERSITY MEDICAL CENTER 

DURHAM, NC 27710 

HE, YONGQUN, DVM, PHD 

ASSOCIATE PROFESSOR 

DEPARTMENT OF MICROBIOLOGY AND IMMUNOLOGY 

CENTER FOR COMPUTATIONAL MEDICINE 

AND BIOINFORMATICS 

UNIVERSITY OF MICHIGAN MEDICAL SCHOOL 

ANN ARBOR, MI 48109 

HUANG, SUSAN S., MD, MPH 

PROFESSOR 

DIVISION OF INFECTIOUS DISEASES 

UNIVERSITY OF CALIFORNIA, IRVINE 

ORANGE, CA 92868 

KIMA, PETER E., PHD 

ASSOCIATE PROFESSOR 

DEPARTMENT OF MICROBIOLOGY 

AND CELL SCIENCES 

UNIVERSITY OF FLORIDA 

GAINESVILLE, FL 32611 

MESHNICK, STEVEN RICHARD, MD, PHD 

PROFESSOR AND ASSOCIATE CHAIR 

DEPARTMENTS OF EPIDEMIOLOGY AND MICROBIOLOGY 

AND IMMUNOLOGY 

GILLINGS SCHOOL OF GLOBAL PUBLIC HEALTH 

UNIVERSITY OF NORTH CAROLINA 

CHAPEL HILL, NC 27599 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PARRISH, COLIN R., PHD 

PROFESSOR 

DEPARTMENT OF MICROBIOLOGY AND IMMUNOLOGY 

JAMES A. BAKER INSTITUTE 

COLLEGE OF VETERINARY MEDICINE 

CORNELL UNIVERSITY 

ITHACA, NY 14853 

ROY, CRAIG R., PHD 

PROFESSOR AND VICE CHAIR 

SECTION OF MICROBIAL PATHOGENESIS 

BOYER CENTER FOR MOLECULAR MEDICINE 

YALE UNIVERSITY 

NEW HAVEN, CT 06536 

SCHOOLEY, ROBERT TURNER, MD * 

PROFESSOR 

DIVISION OF INFECTIOUS DISEASES 

UNIVERSITY OF CALIFORNIA, SAN DIEGO 

SAN DIEGO, CA 92023 

STEVENSON, BRIAN, PHD 

PROFESSOR 

DEPARTMENT OF MICROBIOLOGY AND IMMUNOLOGY 

UNIVERSITY OF KENTUCKY COLLEGE OF MEDICINE 

LEXINGTON, KY 40536 

TORTORELLA, DOMENICO, PHD 

ASSOCIATE PROFESSOR 

DEPARTMENT OF MICROBIOLOGY 

MOUNT SINAI SCHOOL OF MEDICINE 

NEW YORK, NY 10029 

ZWICK, MICHAEL EDWARD, PHD * 

ASSOCIATE PROFESSOR 

DEPARTMENT OF HUMAN GENETICS 

EMORY UNIVERSITY SCHOOL OF MEDICINE 

ATLANTA, GA 30322 

SCIENTIFIC REVIEW OFFICER 

BUCZKO, ELLEN S., PHD 

SCIENTIFIC REVIEW OFFICER 

SCIENTIFIC REVIEW PROGRAM 

DIVISION OF EXTRAMURAL ACTIVITIES 

NATIONAL INSTITUTES OF HEALTH/NIAID 

BETHESDA, MD 20892 

EXTRAMURAL SUPPORT ASSISTANT 

CRAWFORD, KAMESHA C. 

PROGRAM SPECIALIST 

SCIENTIFIC REVIEW PROGRAM 

DIVISION OF EXTRAMURAL ACTIVITIES, NIAID/NIH/DHHS 

ROCKVILLE, MD 20892 

PROGRAM REPRESENTATIVE 

ROBBINS, CHRISTIANE M. 

PROGRAM OFFICER 

OFFICE OF THE DIRECTOR 

DIVISION OF MICROBIOLOGY AND INFECTIOUS DISEASES 

NIAID/NIH/DHHS 

5601 FISHERS LANE, ROOM 7G44 MSC 9826 

BETHESDA, MD 20892 

* Temporary Member. For grant applications, temporary members 

may participate in the entire meeting or may review only selected 

applications as needed. 

Consultants are required to absent themselves from the room 

during the review of any application if their presence would 

constitute or appear to constitute a conflict of interest.