NIMML is a team of over 30 researchers that combine computational approaches, pre-clinical and clinical experimentation techniques, and system biology methods in translational immunology to tackle challenges in infectious, immune-mediated and chronic inflammatory diseases. NIMML was founded in 2002, under the guidance of Dr. Bassaganya-Riera and Dr. Hontecillas, with the mission of translating novel, biological knowledge into safer and more effective therapeutics for human diseases. With a growing research funding portfolio exceeding $15 million, over 100 publications, and 20 patents and applications, NIMML strives towards the vision of becoming a world leading research laboratory in translational, personalized, predictive, participatory, and preventive medicine. Through the Center for Modeling Immunity to Enteric Pathogens (MIEP), a NIAID-funded program, NIMML has pioneered pipelines applying high-throughput computational and experimental immunology techniques and system biology approaches in translational immunology research and discovery. NIMML models and simulates in silico trials in order to guide the design novel experiments, validate hypotheses and develop mechanistic and translational insights of human diseases.

1. Developing Safer Cures for Human Diseases
Modeling Immunity
to Enteric Pathogens

2. One integrated unit with the Mission of developing safer and
more effective therapeutics for human diseases

3. Literature mining &
in-house generated data
Creation of the
network
Parameter estimation &
ODEs adjustments
In silico experimentation
Prediction generation
In vivo/vitro validation
Hypothesis testing
Refinement of the model
with new generated data
SYSTEMS
IMMUNOLOGY
APPROACH
Publication!
https://www.nimml.org

4. Multiscale Modeling
https://www.nimml.org

5. > 50,000
Mice Utilized
3TB
Data in Server
> 108
Agents in Models
55,419
Web Site Visits
$12,000,000
Program
> 100/20
Publications/Patents
> 40
Personnel
> 70
MMI Participants
> 150
Undergrads
https://www.nimml.org

6. https://www.nimml.org

7. DRUG DEVELOPMENT
I. Identifying / validating new therapeutic targets & biomarkers
II. Testing mechanism of action, PK/PD, efficacy/safety
III. Human clinical trials
IV. PPARs, NLRs and LANCL2
V. Biotherapeutics Inc.
Binding of Abscisic acid &
NSC61610 with LANCL2
 LANCL2: a new drug target for inflammatory diseases & diabetes.
 We have Identified a diverse range of NLRs that are significantly
altered in colons of IBD patients.
 Targeting NLR signaling represents a promising and novel therapeutic
Binding of punicic acid
with NLRX1
https://www.nimml.org

8. NUTRITIONAL IMMUNOLOGY
I. Identifying dietary compounds with anti-inflammatory effects
II. Mechanisms of interaction: diet, microbiome and immune system
PMID: 23541470
https://www.nimml.org

9. IMMUNE MEDIATED DISEASES
I. Identifying and validating new therapeutic targets
II. Developing computational models of autoimmune disease
 Biologics have limited efficacy and significant side effects.
 LANCL2 ligands have demonstrated greater efficacy and no side effects.
https://www.nimml.org
Severity of Disease
5 ASA
(MAINT)
Cortico-
Steroids
(FLARE UP)
6-MP Immuno
suppressant
(MAINT)
TNFα
(MAINT
FLARE UP)
25 - 40% UC;
66 - 75%
Crohn’s patients
require surgery
Drug development
LANCL2 (New Therapeutic Target)

10. INFECTIOUS DISEASES
Combining experimental & computational methods to study the
mechanisms of mucosal immunoregulation of H. pylori, E. coli,
C. difficile, and influenza virus.
 Novel insights on the immunoregulatory mechanisms underlying
immune responses to H. pylori infection.
https://www.nimml.org

11. CHRONIC DISEASES
I. Characterizing the mechanisms of action & cell specificity
underlying the anti-diabetic actions of LANCL2.
II. Developing & refining novel animal models of T2D & obesity.
III. Investigating the cross-talk between immunity & metabolism.
Guri et al Clinical Nutr (2010) 29: 646-653
AvandiaABA ABA +
Avandia
Control
https://www.nimml.org
 LANCL2: a new drug target for inflammatory diseases.
 Initial efficacy of LANCL2 pathway validated in T2D:
 Novel, effective and safe
 Increased insulin sensitivity through LANCL2 MOA
 Results equivalent to prescription Avandia without side effects

12. COMPUTATIONAL IMMUNOLOGY
I. Building multiscale modeling platforms & HPC driven models
II. Developing predictive, validated computational models
 Systems modeling of molecular mechanisms controlling cytokine-
driven CD4+ T cell differentiation and phenotype plasticity
 Predictive computational modeling of the mucosal immune
responses during Helicobacter pylori infection
https://www.nimml.org
PMID: 24039925
PMID: 25364738
PMID: 23592971

13. COMPUTATIONAL IMMUNOLOGY
I. Building multiscale modeling platforms & HPC driven models
II. Developing predictive, validated computational models
III. Using computational modeling to accelerate drug development
https://www.nimml.org

14. https://www.nimml.org

15. Biotherapeutics Inc.
A NIMML/VT Biotech Spin off
The company
Funded in 2008 with the goal of developing
small molecule drugs to treat diabetes and
inflammation
Technology Platform
Extensible therapeutic pipeline to treat
pathologies based on a unique MoA
Targeted Markets
Initial two markets: the T2D market
($38B) and the IBD market ($8B)
Products
Identified several Top Lead Compounds that
are advanced towards IND filing with the FDA.
Excellent competitive advantage
Outreach & BD
In discussions with 3 TOP10 Pharma
companies and VC groups. Presence at
BIO and JP Morgan Healthcare
conferences
Milestones and Funding
Closed seed funding round of over $1.5M. Next
round: $5-10M to prepare IND enabling data to
submit to FDA to start human trials
Job Creation
The company is recruiting and contributing to high
quality job creation in Virginia. Employing VT
graduates
Developing Safer Therapies from Nature’s
Innovations
https://www.nimml.org