A summary of the Petriz lab research interests
Summary of our Research:
The
ability to bridge large-scale and single-cell approaches at a
functional level are key to identify biomarkers expressed on rare
cells. We translate biomedical science into integrated clinical
practice and public health by using certified transference
processes in cooperation with trusted allies and partners
supporting biomedical research. More specifically, we are
interested in investigating and developing experimental approaches
key to understand the principles underlying the emergence and
prevention of cancer therapy resistance.
Description of our Research:
Our lab utilizes cutting-edge cellular-based research tools on a
new view of the characterization of cells and subcellular
compartments, involving the use of fluorescent tracers coupled with
measurements for detecting antigens or markers, a particular
nucleic acid sequence, enzymatic activities, the regulation of
protein function through conformational modulation, or the role of
multidrug resistance transporters as epigenetic interplayers.
Functional cytomics enables discovery and characterization of novel
cell subsets, mechanisms of resistance to immunotherapy and
chemotherapy, and multiplexed measurements of cells for detecting
the presence or absence of malignant clones at a single-cell level.
We are mainly focused on the cellular and molecular mechanisms
controlling the proliferation and differentiation of leukemic stem
cells. We are particularly interested in how these mechanisms
operate at different disease refractory processes within
hematological malignancies.
Since more than three decades, we study the implications of
multidrug resistance transporters in stem cell biology. The cancer
stem cell (CSC) model has been established as a cellular mechanism
that contributes to phenotypic and functional heterogeneity in
diverse cancer types. Recent observations, however, have
highlighted many complexities and challenges: the CSC phenotype can
vary substantially between patients, tumours may harbour multiple
phenotypically or genetically distinct CSCs, metastatic CSCs can
evolve from primary CSCs, and tumour cells may undergo reversible
phenotypic changes. Although the CSC concept will have clinical
relevance in specific cases, accumulating evidence suggests that it
will be imperative to target all CSC subsets within the tumour to
prevent relapse. In cancer therapy, detailed understanding of the
effects of drugs on signal transduction pathways in the target
cells is of pivotal relevance in tailoring individualized
therapeutic approaches. Furthermore, new and more detailed
diagnostics will help to specifically design a therapy for the
individual patient.
The group focuses on interdisciplinary projects that cover basic
biology through to practical biomedical applications through the
measurement of human cancer cells. Our ongoing research projects
cover innovative approaches to study the expression of primitive
stem cell markers during origin, progression, maintenance of cancer
and its management; the quality and safety assessment of
hematopoietic blood progenitor and stem cell grafts; the role of
myeloid derived suppressor cells in immunotherapy and targeted
therapy for clinical decision-making; new cytomic strategies for
whole blood and marrow immunostaining; the use of natural compounds
for cancer treatment; and the accurate detection and significance
of minimal residual disease in acute leukemia. We are currently
evaluating evidence of mechanisms by which ABC transporters
differentially activates low- or high-level transduction cell
signaling and their potential role as epigenetic interplayers to
protect and mitigate the stem cell compartment from therapeutic
damage.
Research is now well underway to develop sophisticated methods for
identifying patient populations who will most likely respond to
specific interventions. While we have made significant strides in
cancer research over the past two decades, there is plenty of work
left to do and make “visible the invisible”. Cancer stem cells are
rare and elusive cells and our research is critical for developing
new experimental strategies to evaluate the cellular response to
anticancer therapies. We are committed to accelerate the
application of new sophisticated cytomic strategies and,
importantly, uniquely placed to improve prevention, diagnosis,
prognosis, therapy, and the health of patients of all
ages.
Main
scientific, technical or innovation applications of our
work
Following
sample preparation, a cytomic assay is typically straightforward,
less time-consuming, less labour-intensive than other cellular
multiplexing assays, and aimed at to determine the molecular
phenotype of single-cells. New methods to identify, characterize,
isolate, expand, target and track CSCs and test their relevance in
clinical prognostic and treatment settings offer the possibility of
major advances in cancer prevention and treatment. Progress is
currently limited by lack of: coordinated, consensus methods,
consistent mechanisms to accrue and access patient samples, and the
ability to apply investigative methods and share material and data
on a large scale.
Main scientific, technical or innovation applications of our work
will help to:
• Provide access to new and expanded resource and technology
platforms essential to accelerate breakthroughs in cancer
prevention, diagnosis and treatment that develop or exploit new
knowledge about CSC populations.
• Enable storage and sharing of biological samples and data using
defined methods that meet common standards and are readily
transportable.
• Facilitate exchange and cross-training of investigators and
support staff engaged in CSC research at all levels and across
disciplines.
• Promote the development of new technologies that support the
discovery and translation of CSC-relevant research as a critical
step in changing the prevention and management of cancer.
• Help laboratory personnel to identify, acquire, and implement the
appropriate software to analyze adequately the growing number of
complex datasets in flow cytometry.
Main scientific, technical or innovation applications of our work
will help to:
Following
sample preparation, a cytomic assay is typically straightforward,
less time-consuming, less labour-intensive than other cellular
multiplexing assays, and aimed at to determine the molecular
phenotype of single-cells. New methods to identify, characterize,
isolate, expand, target and track CSCs and test their relevance in
clinical prognostic and treatment settings offer the possibility of
major advances in cancer prevention and treatment. Progress is
currently limited by lack of: coordinated, consensus methods,
consistent mechanisms to accrue and access patient samples, and the
ability to apply investigative methods and share material and data
on a large scale.
• Provide access to new and expanded resource and technology
platforms essential to accelerate breakthroughs in cancer
prevention, diagnosis and treatment that develop or exploit new
knowledge about CSC populations.
• Enable storage and sharing of biological samples and data using
defined methods that meet common standards and are readily
transportable.
• Facilitate exchange and cross-training of investigators and
support staff engaged in CSC research at all levels and across
disciplines.
• Promote the development of new technologies that support the
discovery and translation of CSC-relevant research as a critical
step in changing the prevention and management of cancer.
• Help laboratory personnel to identify, acquire, and implement the
appropriate software to analyze adequately the growing number of
complex datasets in flow cytometry.
Main
social impact features of our work
The
patient’s condition can change dramatically in a short period of
time due to treatment and illness. Complications developed by these
patients are known to have better outcomes with earlier
identification and management, and collaboration between different
supporting disciplines is of great importance. Given that current
clinical application of functional cytomics remains largely
confined to few specific academic centers, our goal is to provide
the patients with a wide range of scientific support strategies,
through precision, oversight and accuracy to integrate:
• Clinical implementation of functional cytomic asays.
Precision/personalized high-quality assays for individual patients,
by integrating functional cytomics to accelerate new experimental
approaches for ex vivo and in vivo drug sensitivity.
• Translation of functional screening into novel clinical
strategies. Measure the impact of exogenous interventions such as
drug exposure on tumor cell phenotype. Functional screening deliver
precise cytome information regarding the capacity of drugs to
elicit apoptotic responses/drug resistance of cancer cells without
a prior knowledge of the molecular mechanistic underpinnings of
such responses.
• The understanding of drug resistance and the prediction of
effective drug combinations. Examples include strategies to tackle
resistance to tyrosine kinase inhibitors in a rare population of
cancer stem cells named the "side population" from patients with
chronic myelogenous leukemia, myelodisplastic syndromes, acute
leukemia, and other malignant hematologic diseases that affect
patients of all ages.
• The reduction of costs by obtaining specialized instrumentation
and personnel for execution of cytomic screens in partnership with
stakeholders and biotechnological partners.
• Functional and immunophenotyping data sets aimed at understanding
complex functional-to-phenotype correlations and, thereby,
accelerate discovery of the biology of leukemogenesis as well as
the clinical implementation of novel
therapies.
Three questions we are trying to answer with our
research:
• What defines a stem cell in functional and phenotypic
terms?
• How can we both evaluate and reverse drug/immunotherapy
resistance?
• Why should we care about the oxygen in the metabolic/tumour
microenvironment?
What
do we think are the most important social impact results of our
work?
Cancer
is a complex group of diseases with serious implications not just
for individuals and their families, but also for society in general
and health a system in particular, remains an important health
challenge. Patients can respond differently to the same medicine,
and many patients do not benefit from the first drug they are
offered in treatment. Because personalized medicine is able to
provide the right therapy, in the right dose, improving patient
stratification and prediction of disease, we expect to make
available:
• Better diagnosis and earlier intervention. Cytome analysis could
determine precisely whether patients are susceptible to drug
toxicities, and choose the optimal treatment strategy.
• Individualized drug selection. Here we consider which molecular
and functional models best predict how a patient will respond to a
therapy to develop accurate and cost-effective tests. Clinicians
will have fundamental information for decision-making and select
the optimal care. In addition, functional testing could help to
select the best drug usage and schedule or combination, when
indicated, with anticancer natural products.
• Drug development challenges. A better understanding of clinical
observations made during individualized drug development and
conventional therapy will help to identify new disease subtypes and
their associated molecular pathways, and design drugs that target
them with more efficient trials. Cytome analysis could also help to
select patients for inclusion in, or exclusion from, and assay new
drugs medicines that might otherwise be abandoned considered being
ineffective in non-individualized patient populations.
Keywords
Cytometry, stem cells, cancer stem cells, fluorescence, toxicology,
pharmacology, immunotherapy, cytome, phenotype, drug discovery,
high-content analysis, data mining, high-throughput screening,
bioinformatics, human cytome project.