New projects are continually added to this list. Be sure to scroll down the list to see the latest additions.
EXINC MMU 001: Chlamydia Vaccine:
These novel recombinant Chlamydial proteins,
alone or in combination, are suitable immunogens for a vaccine formulation to prevent Chlamydia infections in humans.
Show Details
Chlamydias are major disease-causing agents of infection affecting
over 61 million individuals worldwide. Genital tract infection with
Chlamydia trachomatis, the most common sexually transmitted
bacterial disease, is an escalating global public health concern
causing considerable morbidity and socioeconomic burden
worldwide. Although antibiotics are used to treat symptomatic
urogenital infections, chlamydial infection remains asymptomatic in
approximately 50% of infected men and 70% of infected women
contributing to horizontal transmission between sexual partners.
There is no commercially available vaccine for the prevention of
Chlamydia infections in human.
Researchers have evaluated novel Chlamydial proteins as
immunogens in animal models for their ability to induce a protective
immune response. Results indicate that these proteins are suitable
candidates for a vaccine formulation.
EXINC MMU 002: Method for Determining Coagulation Activation in Whole Blood:
Measuring coagulation activation, including thrombin generation, is useful in a number of clinical conditions.
Researchers have developed a novel method and class of substrates to do this using whole blood, for instance from a finger prick,
using conventional fluorescence equipment.
Show Details
Applications:
Generate a point-of-care thrombin generation curve in
the absence of anticoagulants in whole blood. Thrombin
generation curves are known to be altered in different
disease states.
This novel method can be used as a point-of-care test for
the presence of novel oral anticoagulants (NOACs),
namely rivaroxaban, apixaban, and dabigatran in blood.
Detect disorders of coagulation at point-of-care
Screen for inhibitors of coagulation in whole blood
EXINC MMU 003: Biomarkers of CF for Better Screening and Therapeutic Treatments:
A panel of CF-specific biomarkers from blood spot extracts and sweat samples for CF screening and
guide discovery of new molecular targets.
Show Details
Cystic fibrosis (CF) is a complex multi-organ disease that is among the
most common life-shortening genetic disorders affecting the western
world. Mutations to the cystic fibrosis transmembrane conductance
regulator (CFTR) gene results in abnormal secretory glands that impact
respiratory, digestive, and reproductive systems of CF patients. Newborn
screening for early detection of CF currently relies on population-based
genetic testing, but lacks specificity resulting in false-positives and
widespread carrier identification, which contributes to unnecessary
follow-up testing. Thus, new biomarkers are urgently needed to improve
the performance of CF screening that may also serve to predict disease
progression and treatment responses to therapy on an individual level.
The discovery is related to the identification of a panel of CF-specific
biomarkers from blood spot extracts and sweat samples. Using tandem
mass spectrometry (MS/MS) capabilities, nontargeted metabolite
screening of CF patients revealed new metabolites and their aberrant
metabolic pathways from asymptomatic infants. Retrospective analysis
suggests that this technology is selective and sensitive to identify and
stratify CF patients early in life based on their characteristic metabolite
profile that is complementary to genotyping and sweat chloride testing.
Additionally, a new therapeutic target for CF therapy may avoid recurrent
lung infections has been discovered that is orthogonal to orphan drug
development largely based on CFTR modulation therapy.
EXINC MMU 004: Comprehensive Antibiotic Resistance Database:
A bioinformatic database of resistance genes, their products and associated phenotypes.
Resource for antimicrobial resistance (AMR) surveillance in healthcare, agriculture and environmental settings.
Show Details
The Comprehensive Antibiotic Resistance Database (CARD)
is an ontology- and model-based framework for detection
of antibiotic resistance genes. It contains an expert-curated
collection of characterized, peer-reviewed resistance determinants
and associated antibiotics, organized by the Antibiotic Resistance
Ontology (ARO) and AMR gene detection models. The software
utilizes these detection models for predicting AMR from genome
sequences.
Other associated tools include the Resistance Gene Identifier (RGI)
which is a novel genome analysis tool for resistome prediction. It
annotates DNA and protein sequences and detects matches to
CARD reference sequences, variants of known AMR genes and
emergent threats.
Resistomes is a computer-generated data set including genome
annotation and variants data using RGI for 85 pathogens of interest.
For each of these pathogens, complete chromosome sequences,
plasmid sequences, and whole genome shotgun assemblies were
analyzed individually by RGI to generate prevalence data. Results
are further categorized using the ARO.
Benefits
Expert-curated database that is updated monthly
As of November 29, 2019:
4358 Ontology Terms, 2909 Reference Sequences, 1318
SNPs, 2663 Publications, 2943 AMR Detection Models
Resistome predictions: 85 pathogens, 8046
chromosomes, 18337 plasmids, 90531 WGS assemblies,
182532 alleles
Software for prediction of resistance genes from isolates
or metagenomic samples from clinical, environmental, or
agricultural samples
EXINC MMU 006: Treatment of Breast Cancer:
Dronedarone is an FDA-approved drug that has shown anti-cancer activity in breast cancer cell cultures, sphere forming assays and in mice.
Show Details
Effective and well-tolerated novel therapies are
needed for the treatment of breast cancer and other
cancers. Unfortunately, the length of time required to
develop a new drug is increasing, averaging
approximately 14 years and costing US$1.8 billion. This
long development period and high cost of new
oncology drugs is largely due to unexpected problems
once they reach testing in human clinical trials.
Although drugs may appear to be effective in cell
cultures and/or animal models, they often cause
unacceptable toxic side effects in humans.
Dronedarone is an FDA-approved oral drug that is used
to treat patients with cardiac arrhythmias but has
shown to anti-cancer activity in breast cancer cell
cultures, sphere forming assays and in mice. Given its
established safety profile and pre-clinical efficacy data,
Dronedarone offers a tantalizing opportunity for drug
re-purposing as a potential anti-cancer agent, primarily
through its effects on the induction of apoptosis and
MYC inhibition.
Dronedarone and related
compounds (which are structurally similar and likely to
have comparable safety profiles) hold promise as novel
anti-cancer agents for the treatment of patients with
breast and other cancers.
EXINC MMU 007: Plant Derived Pharmacological Chaperones for Treatment of PKU:
These plant-derived natural products offer a safe, yet effective, therapeutic treatment of PKU via nutritional supplementation.
Show Details
Pharmacological chaperones (PCs) are a promising strategy for
the treatment of genetic disorders based on enzyme
enhancement therapy, such as phenylketonuria (PKU). PKU is a
common in-born error of amino acid metabolism that is related
to more than 500 disease-causing mutations of phenylalanine
hydroxylase (PAH) or by a defect in the synthesis or regeneration of tetrahydrobiopterin (BH4). To date, lifelong dietary
Phe-restriction and BH4 supplementation are the only accepted
treatment options for PKU patients. However, special lowprotein diets can lead to malnutrition, psychosocial or
neurocognitive complications due to poor compliance, while BH4
therapy is costly and only 20-30% of PKU patients are responsive.
Using a novel screening strategy to identify small
molecules from a chemical library with chaperone activity,
plant-derived natural
products (and synthetic analogs) have been identified to enhance the activity of
denatured/inactive wild-type PAH and two clinically relevant PKU
mutant enzymes. These plant-derived natural products are
present in variable amounts in the human diet and thus offer a
safe yet effective therapeutic treatment of PKU via nutritional
supplementation, notably for patients with severe phenotypes.
EXINC MMU 008: Laboratory Scores for Risk Stratification of Patients with Possible Cardiac Injury:
Using important biochemical parameters to accurately determine the risk of an acute cardiovascular event or death with easy interpretation.
Show Details
Though cardiovascular disease resulting in heart attacks is a major cause
of morbidity and mortality worldwide, most patients with chest pain
symptoms presenting to the emergency department (ED) do not have a
heart attack. However, there is no easy way to accurately identify which
patients are at low or high risk of an acute cardiovascular event or death.
The current hospital-based lab test to identify myocardial injury in
patients uses a biomarker (i.e. cardiac troponin) that is not exclusively
elevated with cardiac infarction, leading to misdiagnoses that can miss
patients who need treatment and possibly admit patients for invasive
tests and treatment who could be sent home.
A method has been developed to accurately
determine the risk of an acute cardiovascular event or death that
incorporates important biochemical parameters for easy interpretation.
At least two different laboratory scores have been derived for both
clinical and community settings, providing the safest approach to date to
rule out heart attacks or death as soon as a patient comes to the ED.
This also identifies those low risk patients that can be released after
initial bloodwork, which is not possible using other diagnostic pathways.
EXINC MMU 010: Sepsis Prognostic Tool to Create Personalized Mortality Risk Profiles:
A predictive algorithm for assessing personalized sepsis-related mortality risk profiles of septic patients
with utility for both clinical trials and patient care.
Show Details
Sepsis (or “blood poisoning”) is a leading cause of death in
intensive care units (ICUs), with mortality rates as high as 35%.
Previous clinical trials in sepsis utilized a “one size fits all” approach
which has not translated into improved outcomes. Better
strategies for patient care and clinical trial enrichment, including
prognostic enrichment (enrolling patients at highest risk of death)
and predictive enrichment (enrolling patients who are more likely
to respond to treatment based on pathological differences), are
needed.
A personalized tool has been developed for assessing the mortality
risk of septic patients with utility for both clinical trials and patient
care. It is a highly reliable predictive algorithm of sepsis-related
mortality based on monitoring a specific combination of biological
and clinical indicators over time. A mortality risk profile can be
generated for each individual patient, highlighting the relative
contribution of each indicator to the risk of death. This can help
identify underlying pathophysiology of each patient to inform
treatment decisions and monitor their response to treatment.
EXINC MMU 011: Antibiotic Resistance Platform Assay to Measure Factor Xa Inhibitors in Blood and Plasma:
The antibiotic resistance platform (ARP) can be used for both the identification of antibiotic adjuvants and for antibiotic dereplication.
Show Details
Solving the antibiotic resistance crisis requires the discovery of
new antimicrobial drugs and the preservation of existing ones.
With no new antibiotics on the horizon, blocking resistance with
antibiotic adjuvants have emerged as a viable strategy. Antibiotics
are co-formulated with an inhibitor of resistance, blocking the
resistance element and freeing the antibiotic to target the
bacterium. A major difficulty in identifying new antibiotics is the
frequent rediscovery of known compounds, necessitating laborious
"dereplication" to identify novel chemical entities.
The antibiotic resistance platform (ARP) can be used for both the identification of antibiotic
adjuvants and for antibiotic dereplication. The ARP is a cell-based
library of Escherichia coli expressing mechanistically distinct
individual resistance elements in an identical genetic background.
The strength of the ARP lies within the mechanistic diversity and
rigorously curated substrate specificity of the resistance strains.
Using either a low copy plasmid or integration of the gene into the
bacterial chromosome, the researchers are able to control
resistance gene copy number. Expression is further regulated
through the use of two promoter systems differing in strength.
This platform is optimized for antibiotic dereplication and the
identification of potentiators of existing antibiotics.
EXINC MMU 012: Assay to Measure Factor Xa Inhibitors in Blood and Plasma:
This assay can test both plasma and citrated whole blood to allow for simple, on-demand usage in hospital labs.
Show Details
Anti-factor Xa direct oral anticoagulants (aFXa-DOACs), such
as rivaroxaban and apixaban, represent a new class of drug
being used more frequently in the treatment and prevention
of arterial and venous thrombosis. As such, it is becoming
more important to be able to measure the levels of these
agents in the blood of patients. However, there is currently
no simple way to accurately quantify circulating levels of
aFXa-DOACs, particularly at very low concentrations.
This technology provides an assay to quickly and
conveniently determine levels of aFXa-DOACs directly in
whole blood or plasma.
EXINC MMU 013: Laboratory Score for Predicting Cardio-Toxicity:
A novel algorithm to detect risk of cardio-toxicity using a combination of easily detectible cardiac biomarkers in the blood.
Show Details
Minimizing the risk of cardio-toxicity is an essential
consideration in tailoring medical treatments involving anticancer therapy. Current methods of cardio-toxicity
management and detection are based on physical
examination, assessment using echocardiography, and
endomyocardial biopsy. Unfortunately, these methods
either have low diagnostic sensitivity, low predictive power
in detecting subclinical myocardial injury, or are impractical
due to invasiveness. These methods only identify cardiac
damage after the onset of cardiac dysfunction. Thus, a novel
algorithm to detect risk of cardio-toxicity is advantageous,
using a combination of easily detectible cardiac biomarkers
in the blood.
EXINC MMU 015: Local Infusion of Immuno-Therapeutics (LIIT):
A platform technology with hydrogels that can sustain and localize antibody/protein release, relevant to a wide variety
of clinical applications.
Show Details
Protein and antibody therapeutics are becoming an increasingly
prevalent class of drugs due to their selectivity and potency
compared to small molecule drugs. However, administration and
delivery are challenging due to their pharmacokinetic properties
such as uptake at disease sites, half-life, tissue distribution,
elimination. Currently, repeated and frequent intravenous doses or
infusions are required to achieve therapeutic benefit. For example,
bispecifics are continually infused for several weeks. Therefore,
there is a need for improved methods of delivery for these protein
and antibody therapeutics.
Hydrogels are an ideal vehicle for drug delivery since they are
injectable, biocompatible and hold large drug payloads with
enhanced protein stability. Currently, their use clinically has been
limited because they only marginally decrease injection frequency.
A platform technology
with hydrogels that can sustain and localize antibody/protein
release for several weeks is available. Ongoing work with this platform
technology includes pre-clinical mouse studies in a glioblastoma
model.
EXINC MMU 016: Adenovirus Spray Drying:
A robust method for preparing a thermally stable adenovirus formulation, extending the possible applications of
adenovirus-based vectors as thermally stable vaccines.
Show Details
Adenovirus-based gene transfer vectors are being increasingly
developed as promising vaccine platforms against both old and
newly emerging infections1-3
. However, the real-world application
of adenoviral vectors, particularly in developing countries, is
challenging due to their instability when stored or transported at
even mild temperatures. The cold chain requirements for
maintaining stability increase the vaccine’s cost and create logistical
challenges for distribution and storage. A promising approach
capable of increasing thermal stability is through vitrification with
excipient matrices, preferably by spray drying due to scalability and
favorable economics. Simple excipient formulations appear poorly
suited to stabilizing the viral vector and more complex formulations
yielding a well-stabilized spray dried form had yet to be developed
until the present invention.
A robust method for preparing a thermally stable adenovirus
formulation has been developed through the immobilization of
adenoviral vectors in a multi-component non-cytotoxic
carbohydrate matrix by spray drying. This work extends the possible
applications of adenovirus-based vectors as thermally stable
vaccines.
EXINC MMU 017: Novel Compounds for Reversing Β-Lactam Resistance in MRSA:
Novel antimicrobial compounds of new chemical class and new mode of action for therapeutics as monotherapy or
in combination with other antibiotics for reversing beta-lactam resistance in MRSA.
Show Details
Staphylococcus aureus is the leading cause of both hospital and
community-associated infections worldwide and a major cause of
morbidity and mortality due to the emergence of methicillinresistant S. aureus (MRSA). The pipeline for innovative antibiotics
is insufficient to overcome this healthcare threat and, thus new
strategies are urgently needed.
Using a cell-based screen of ~45,000 diverse synthetic compounds,
researchers discovered a potent bioactive
(MAC-545496) that reverses β-lactam resistance in the
community-acquired MRSA USA300 strain. This compound
attenuates the MRSA virulence in vivo with potency at the low
nanomolar range, inhibits biofilm formation, and abrogates
intracellular survival in macrophages. Mechanistic characterization
through chemical-genomics and biochemical approaches revealed
the cellular target to be GraR (glycopeptide resistance associated
protein R), an important virulence factor and antibiotic resistance
determinant. This newly discovered small molecule bioactive is the
first inhibitor against GraR; it can serve as: (i) an antibiotic adjuvant
reversing methicillin resistance; and (ii) an anti-virulence agent
effective as a monotherapy in vivo against MRSA. Together, this
work provides a novel antibacterial lead series of new mechanism
to combat drug-resistant Staphylococcal infections.
EXINC MMU 021: Antibacterial Phage Hydrogels:
A self-healing and autofluorescent hydrogel made entirely of bacteriophage can be used for a variety of medical and environmental applications.
Show Details
Bacteriophages (also known as phages) are viruses that specifically fight
bacteria in nature, without affecting non-bacteria cells. Bacteriophages have
been used for over 100 years in clinics around the world to treat bacterial
infections. With the rise of superbugs, phages have garnered more attention
as a targeted approach to fight antimicrobial resistant bacteria.
Phages have been developed as structural material for developing coatings
and gels, but the focus has so far never been on their antimicrobial property,
but rather their identity as protein nanoparticles. Therefore, no effort was
made to preserve phage antimicrobial activity when it was used as structural
material.
Researchers have created hierarchically structured
hydrogels composed entirely of self-organized phage. These phage hydrogels
retain the innate antimicrobial activity of free phage and in addition, they can
return to its original state after being cut or sheared with minimal scarring
(self-healing). These bioactive hydrogels also biodegrade and emit
fluorescence, allowing non-destructive imaging. These simple and versatile
hydrogel compositions can be utilized within a plethora of medical and
environmental applications.
EXINC MMU 022: Non-invasive Diagnosis and Treatment Monitoring of Inflammatory Bowel Disease:
A reliable, low-cost method for the diagnosis of Crohn’s disease and ulcerative colitis using urinary biomarkers offering a minimally
invasive strategy for early detection.
Show Details
Inflammatory bowel disease (IBD), including Crohn’s disease (CD)
and ulcerative colitis (UC), is an idiopathic chronic gastrointestinal
(GI) condition that affects pediatric populations with about 20-
30% of IBD patients experiencing their first symptoms before the
age of 18. Current procedures dedicated to diagnosing the disease
rely on invasive and expensive endoscopic imaging and tissue
biopsies that can lead to indeterminate results. New insights into
the distinctive pathophysiology of IBD are critical for early
detection and optimal treatment strategies for individual patients.
Researchers have developed a method to differentiate
between UC and CD through a urinary sample. Researchers have
determined distinct urine-based biomarkers and metabolic
phenotypes of IBD patients thereby permitting differentiation
between CD and UD. This allows for earlier diagnosis and the
facilitation of treatment monitoring while also potentially
avoiding the need for invasive colonoscopic imaging and tissue
biopsies.
EXINC MMU 025: Serum Biomarkers for Early Detection of Peripheral Artery Disease:
A novel panel of PAD-specific biomarkers from serum for the early detection of PAD in asymptomatic patients.
Show Details
Peripheral artery disease (PAD), a form of atherosclerosis manifested in
the lower extremities, is associated with higher risk of cardiovascular
events such as myocardial infarction, stroke, and vascular death. If left
untreated, patients progress to more advanced stages of PAD known as
chronic limb-threatening ischemia (CLTI), which is characterized by rest
pain, non-healing ischemic ulcers, and gangrene requiring limb
amputation. Currently, specialized equipment based on ankle brake
index (ABI, not available in most clinical centres) and clinical symptoms
(e.g, self-reported pain short distance to walk) are used together to
derive a Rutherford score which is used to stage PAD – however, this
approach is more subjective, variable and not convenient for routine
screening and early detection of PAD.
PAD disease progression is highly variable and some CLTI amputee
patients present with no PAD symptoms 6 months before onset. With a
low survivorship amongst CLTI patients, there is an urgent need to
understand the mechanisms of PAD progression for early detection of
CLTI that also guides evidence-based treatment decisions.
Researchers have developed a screening strategy that utilizes
serum biomarkers that differentiate late-stage CLTI from early onset
intermittent claudication (IC). This discovery may enable better risk
assessment and diagnostic testing for PAD that may progress to more
serious CLTI that is often diagnosed late requiring surgical intervention
and amputation with poor clinical prognosis.
EXINC MMU 026: Brush Amphiphilic Block Copolymers for Drug Delivery:
Brush amphiphilic block copolymers for drug delivery and other biomedical applications.
Show Details
Block copolymers based on poly(ethylene glycol) (PEG) and poly(lactic
acid) (PLA) or poly(lactic-co-glycolic acid) (PLGA) have been widely
used in a range of biomedical applications, including tissue
engineering, drug delivery, bioresorbable sutures and implantable
devices. This widespread use is mainly due to the hydrophobicity and
degradability of PL(G)A (enabling its self-assembly in water and
potential to load and deliver a hydrophobic drug) coupled with the
hydrophilicity and excellent protein repellency of PEG. However, the
chemical nature of the polymer inherently limits its potential for
functionalization to adapt to a broad variety of potential applications.
Researchers have developed brush amphiphilic block
copolymers (hydrophobic + hydrophilic properties) based on polymers
that have PL(G)A and PEG blocks not in their backbone (like
conventional PL(G)A-PEG materials) but rather on their side chains.
This results in a polymer that has the same beneficial self-assembly
and protein repellency properties of PL(G)A-PEG but with the capacity
to easily (and inexpensively) tune the chemistry of one or both of the
hydrophilic and hydrophobic phases. This added variability in the
physical properties of these materials can be leveraged for optimizing
a variety of biomedical technologies.
EXINC MMU 027: Printable Enzyme-Stabilizing Hydrogels for Biosensing and Drug Discovery:
A printable in-situ hydrogel-based drug screening platform for HTS that can discriminate between true and “promiscuous” inhibitors.
Show Details
Immobilization of biomolecules (i.e. proteins, enzymes) has significant
implications in energy production, pharmaceutical synthesis, and drug
screening. More recently, interfacial thin-film hydrogels enabling the stable
encapsulation of enzymes have attracted interest in the biosensing field due
to their potential to be incorporated into high throughput screening (HTS)
screens in which high numbers of small volume samples can be tested.
Traditional HTS methods present various challenges including false-positive
hits and non-specific and/or promiscuous behaviour of compounds, typically
due to aggregates that physically block (rather than biochemically bind to) an
enzyme active site. As a result, time and money are lost chasing false lead
compounds. To-date, there has been limited success in the discovery of
methods to quickly identify these promiscuous compounds and aggregates.
To address this, researchers have developed a printable hydrogelbased drug-screening platform that can immobilize a bioactive biomolecule
and control access to that biomolecule based on the hydrogel pore size. This
approach is highly beneficial in drug discovery and early stage pharmaceutical
testing and analysis because it provides the ability to discriminate between
true enzyme inhibitors and promiscuous inhibitors for lead enzyme-targeting
drugs while significantly reducing (by up to 95%) the amount of sample
required for screening. This saves time and money when conducting HTS
while resulting in significantly fewer false-positive hits. The hydrogel is also
printable using an ink jet printer without requiring external activation.
EXINC MMU 028: Deep Learning Model Predicting Therapeutic Potential of Chemicals:
Deep learning model that predicts the mechanism of action and therapeutic utility of uncharacterized chemical compounds, relevant
pharmaceutical implications for drug re-purposing.
Show Details
In small molecule drug discovery pipelines, identification of
mechanism of action and therapeutic potential of compounds with
known bioactivity is a time-intensive process, often taking years to
arrive at a conclusion. Current methods focus on a single therapeutic
indication (i.e. antibacterial, non-steroidal anti-inflammatory,
anticancer) which are typically hypothesis-driven, intuitive, and slow.
Therefore, there is a need for improved predictive tools in identifying
possible mechanisms of action and therapeutic utilities.
Gene expression studies of a wide variety of cell types have revealed
that various cell systems have complex unique fingerprint responses
to chemical perturbants. Researchers have developed a
deep learning model which predicts the mechanism of action of
chemical compounds based on such microbial fingerprint responses.
This densely connected network uses unique microbial responses to
chemical inputs to map unknown (test set) compounds to a well annotated database (training set) of compounds. By utilizing a
sensitive microorganism reporter, the biological activity inherent in
any drug may be detected, even if it is not an antibiotic.
EXINC MMU 029: Gene signature for predicting progression and prognosis of adrenocortical carcinoma:
Gene signature biomarker for diagnosing the progression and prognosis of adrenocortical carcinoma.
Show Details
Adrenocortical carcinoma (ACC) is an aggressive endocrine
carcinoma with a 5-year survival rate of < 50% [1]. Surgical resection
is the only curative treatment, but 50-80% of patients experience
relapse often with concurrent metastasis [2]. Despite being an
aggressive carcinoma, ACC has variable prognosis with some tumors
not recurring or progress slowly to metastasis. Effective assessment
of ACC relapse (progression) and fatality risks is thus critical to
patient or tumor-specific treatment. However, effective risk
stratification remains challenging in ACC, which is even more
difficult considering ACC is an orphan disease with annual incidence
of 1-2 cases/million [3]. Therefore, a method to effectively diagnose
patients with high risk of metastasis and lethal disease is needed.
Researchers have developed a novel multigene
signature panel that robustly predicts ACC prognosis and
progression.
EXINC MMU 030: Gene signature for predicting progression and prognosis of prostate cancer and adrenocortical carcinoma:
Gene signature biomarker for diagnosing the progression and prognosis of prostate and adrenal carcinomas.
Show Details
Prostate cancer (PC) is the top ranked male malignancy in the
developed world. Adrenocortical carcinoma (ACC) is an
aggressive endocrine carcinoma with a 5-year survival rate of < 50%.
For both PC and ACC, surgery remains a main curative
treatment; however, relapse and metastasis are common. To
optimize treatment benefits and reduce fatality, it is essential to
know which cancers are at risk for metastasis and lethal disease.
Therefore, a method to effectively diagnose patients with high risk
of metastasis and lethal disease is needed.
Researchers have developed a novel multigene
signature panel that robustly predicts PC biochemical recurrence
(BCR) as well as ACC prognosis and progression.
EXINC MMU 031: Gene signature for diagnosing kidney and adrenal carcinomas:
Gene signature biomarker for diagnosing the progression and prognosis of kidney and adrenal carcinomas.
Show Details
Clear cell renal cell carcinoma (ccRCC) is the most prevalent and
aggressive type of kidney cancer. Adrenocortical carcinoma
(ACC) is an aggressive endocrine carcinoma with a 5-year survival
rate of < 50%. For both ccRCC and ACC, surgery remains the
main treatment; however, relapse and metastasis are common.
To optimize treatment benefits and reduce fatality, it is
essential to know which cancers are at risk for metastasis and lethal
disease. Therefore, a method to effectively diagnose patients with
high risk of metastasis and lethal disease is needed.
Researchers have developed a novel multigene
signature panel that robustly predicts ccRCC metastasis and fatality
as well as ACC prognosis and progression.
EXINC MMU 032: Novel β-Lactamase Inhibitor:
A unique inhibitor of metallo-β-lactamases that can be used to re-sensitize antibiotic resistant bacteria to β-lactam antibiotics.
Show Details
Resistance to frontline β-lactam antibiotics (penicillins, cephalosporins,
carbapenems) is one of the most pressing public health crises of our
time. β-Lactamases come in two classes, those that use a Ser at their
active site and those that use a Zn2+ metal ion. While inhibitors of Ser βlactamases
are known and routinely used in combination with various βlactam antibiotics in the clinic,
there are no effective inhibitors of
metallo-β-lactamases (MBLs) that can be similarly deployed. These MBLs
have been relatively rare in the clinic, but in the past decade, the
emergence and spread of the NDM alleles of MBLs have gained a
significant foothold and are a pressing clinical concern across the globe.
The MBL enzymes are increasingly common in Gram negative pathogens,
resulting in resistance to virtually all β-lactam drugs, including last resort
carbapenems such as meropenem. They are a particular concern as they
inactivate all penicillin, cephalosporin and carbapenem antibiotics.
Researchers have discovered a potent inhibitor of
NDM and other MBLs through a screen of microbial natural products. The
compound, aspergillomarasmine A (AMA), inactivates MBLs and with the
combination of β-lactam antibiotics it can be used as an effective therapy
to treat infections caused by bacteria harboring MBLs. This combination
offers a solution to a significant unmet medical need. There is ample
precedent for such a drug combination and the market is well
accustomed to such agents. The lack of an effective inhibitor of MBLs
represents an innovation gap that is filled by AMA.
EXINC MMU 034: Thermo-Gel Polymer System for Improved Ophthalmic Drug Delivery:
Schematic of thermo-responsive eyedrops for controlled degradation and sustained drug delivery.
Show Details
Eye drops are the most common and easily administered
form of ophthalmic drug delivery, however, they produce
considerable waste and must be frequently reapplied.
Replacing conventional eyedrops with a hydrogel based
system can improve bioavailability and provide sustained
drug release, however, the mechanical loading from blinking
causes rapid deterioration of the applied gel. Application to
the inferior fornix (the pocket below the lower eyelid) has
been investigated such that the hydrogels do not deteriorate
as quickly while blinking or obstruct vision. However, these
developed systems are often non-degradable, uncomfortable
and difficult to place accurately. Therefore, there is a need
for degradable eye drops that offer prolonged drug release
and simple application.
Researchers have developed a gel formula
consisting of a thermo-sensitive synthetic polymer which
forms a gel when introduced to ocular heat, and the natural
polymer chitosan to improve ophthalmic drug delivery. The
gel degrades over a period of days, during which therapeutic
can be steadily released into the eye. This thermo-gel can be
easily applied to the inferior fornix. By administering the gel
to the inferior fornix non-transparent interventions can be
administered without causing visual impairment.
EXINC MMU 035: 3D Tissues and Assembloids Using Z-Wire Scaffolds:
Scalable production and minimally invasive delivery of functional tissues and assembloids with preserved 3D anisotropic
alignment and spatial organization.
Show Details
Developing engineered tissues and organoids has become a central
focus in regenerative medicine and drug discovery. Currently, there is
a need to create complex functional tissues that resembles the spatial
alignment and organization of native tissues (e.g. aligned and
contractile cardiomyocytes in myocardium, organoid zonation in liver,
etc.). Since current techniques for tissue implantation are invasive and
difficult to implement, there is also a need for the development of
minimally invasive delivery methods of delivery of functional tissues.
Researchers have developed a biocompatible “z-wire”
scaffold as a novel strategy for tissue engineering and organoid
assembly. Through a scalable and gel-free process, the z-wire scaffold
structurally supports the development of cell aggregation and
organoid assembly into a functional tissue construct with precise
spatial organization (e.g. patterning of zone-specific liver organoids to
create hepatic cord assembloids). The z-wire design also reinforces
longitudinal alignment of aggregated cells while allowing
compressibility, which is particularly important for muscle fiber tissues
that require specific biomechanical properties (e.g. cardiac muscle
tissue contractility). These smart scaffolds also incorporate nanoscale
magnetic particles which aid in macroscopic tissue alignment postdelivery by means of external magnetic guidance. These properties
support the intramuscular implantation of functional tissues using
minimally invasive injection.
EXINC MMU 037: Seismic Mitigation Using a Novel Elastomeric Isolator:
A base isolation technology to mitigate the effects of earthquakes on low-rise buildings in high seismic regions.
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Studies of past earthquakes, especially in developing countries, have
shown that numerous deaths are often attributed to the collapse of
poorly constructed housing. If the level of seismic demand, imposed
on these buildings, was reduced through a simple but reliable base
isolation technique, fewer buildings would fail and fewer lives
would be lost. Researchers have developed a prototype isolator to effectively
mitigate the effects of earthquakes on low-rise buildings in high
seismic regions.
This invention bridges the gap between a traditionally fully bonded
elastomer bearing and an unbonded elastomeric isolator. Recent
research has demonstrated the effectiveness of an unbonded fiber
reinforced elastomeric isolator. However, unlike a fully bonded
elastomeric isolator an unbonded isolator cannot resist any (uplift)
tensile forces. Similar to a stable unbonded fiber reinforced
elastomeric isolator, a partially bonded bearing still exhibits a
reduction in horizontal stiffness when displaced laterally. In
addition, the partial bond between the bearing and the contact
surfaces allows the isolator to resist (uplift) tensile forces. Finite
element simulations have confirmed the response characteristics of
a partially bonded bearing.
Results confirm the feasibility of this novel base isolation technique
for hazard mitigation of low-rise buildings located in high-seismic
regions worldwide.
EXINC MMU 038: New Chemistry to Recycle Vulcanized Rubbers Back to Organic Polymers:
A mild and efficient method to recover organic polymers originally used to make a tire which can then be reused to create new products.
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With a global demand for tires expected to reach 3.2 billion units by
2022, we can expect rubber waste from these facilities to increase
as well. Most automotive rubber tires are vulcanized (crosslinked by
sulfur) to make them hard-wearing, and there are no highly efficient
means of converting the rubber back into useful organic polymers.
Instead, these rubbers are used for energy production, processed
into crumb for relatively low value applications or pyrolyzed to make
recover some of the hydrocarbons; in many jurisdictions, they are
collected or sent to land fills.
Researchers have developed a mild and efficient
method to break the sulfur-sulfur bonds that hold these vulcanized
rubbers together to recover the organic polymers originally used to
make the tire; they may be reused to create new products. The
inorganic components in such rubber products (e.g. carbon black,
metal wires, etc.) can also be readily separated and reused for a
variety of applications.