Download 1 HARVARD MEDICAL SCHOOL - PORTUGAL PROGRAM // 4TH

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HARVARD MEDICAL SCHOOL - PORTUGAL PROGRAM // 4TH INTERNATIONAL SYMPOSIUM: IMMUNOMEDICINE
WELCOME MESSAGE
Welcome to the Fourth International Symposium on Immunomedicine of the Harvard Medical School – Portugal
Program in Translational Research and Information.
This year’s symposium will be held on 12-13th April 2013, at the Faculty of Health Sciences of the University of
Coimbra (Coimbra, Portugal).
During the two days of the Symposium there will be seven great talks from invited speakers from Portugal and
Boston, covering many exciting areas in the field of Immunology.
We invite you to join the speakers and the Portuguese and Harvard Medical School Directors of the Program,
whom will be fully available for informal discussions throughout the duration of the Symposium.
We look forward to seeing you all.
_____________________________
______________________________
Maria Carmo-Fonseca
Tom Kirchhausen
Program Director in Portugal
Program Director at Harvard Medical School
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HARVARD MEDICAL SCHOOL - PORTUGAL PROGRAM // 4TH INTERNATIONAL SYMPOSIUM: IMMUNOMEDICINE
KNOW THE SCHEDULE
FRIDAY, 12TH APRIL 2013
4.30pm - 5.30pm
Registration
5.30pm - 6.00pm
Welcome
6.00pm - 7.00pm
Lecture 1: Michael Starnbach
Harvard Medical School
Bacterial Pathogens Modify Host Immunity and Host Cells
7.00pm - 8.00pm
Lecture 2: Margarida Correia-Neves
Escola de Ciências da Ssaúde, ECS UM
Should we care about the thymus during infection by mycobacteria?
8.20pm
Dinner for all those previously registered
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HARVARD MEDICAL SCHOOL - PORTUGAL PROGRAM // 4TH INTERNATIONAL SYMPOSIUM: IMMUNOMEDICINE
day 1
KNOW THE SCHEDULE
day 2
SATURDAY, 13TH APRIL 2013
9.30am - 10.30am
Lecture 3: Nuno Alves
Institute for Molecular and Cell Biology, IBMC UP
The Quest for the Thymus: Molecular and Cellular Mechanisms required for Thymus
Development and Function
10.30am - 11.30pm
Lecture 4: Jonathan Kagan
Boston Children's Hospital, Harvard Medical School
Innate immunity from insects to man
11.30am - 12.00pm
Coffee Break
12.00pm - 1.00pm
Lecture 5: Bruno Silva-Santos
Institute of Molecular Medicine, IMM UL
T cells in cancer and autoimmunity
1.00pm - 2.30pm
Round tables with speakers, including lunch for all those previously registered
2.30pm - 3.30pm
Lecture 6: Margarida Souto-Carneiro
Center for Neurosciences and Cell Biology, CNC UC
B is for Bad: Altered B cell response in primary Immunodeficiencies and
Neurodegeneration
3.30pm - 4.30pm
Lecture 7: Sung-Yun Pai
Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Med. School
Translational Investigation in Congenital Immunodeficiency
4.30pm - 5.00pm
Coffee Break
5.00pm - 6.45pm
Research as a Career in Biomedicine: Why it is Fun
Open Discussion with Speakers and HMS-PT Directors
6.45pm - 7.00pm
Farewell
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HARVARD MEDICAL SCHOOL - PORTUGAL PROGRAM // 4TH INTERNATIONAL SYMPOSIUM: IMMUNOMEDICINE
MEET THE SPEAKERS
lecture 1
MICHAEL STARNBACH
Bacterial Pathogens Modify Host Immunity and Host Cells
Research in my lab uses a combination of cellular and molecular
approaches in the analysis of cellular immune responses to pathogens
that cause chronic bacterial infections. Many virulence factors have been
identified that allow bacteria to survive and replicate within the
mammalian host and often within host cells. I have focused on the
immune consequences of these survival strategies, specifically asking the following questions:
What are the pathways for recognition of antigens from intracellular bacterial pathogens?
How do bacterial virulence factors subvert or inhibit cellular immune responses allowing for chronic infection?
How can we promote the recognition of bacterial antigens that may or may not be recognized in the context of
natural infections?
What are the key host effector cells and pathways needed for protective immune responses to intracellular
bacterial pathogens and their products?
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HARVARD MEDICAL SCHOOL - PORTUGAL PROGRAM // 4TH INTERNATIONAL SYMPOSIUM: IMMUNOMEDICINE
MEET THE SPEAKERS
lecture 2
MARGARIDA CORREIA-NEVES
Should we care about the thymus during infection by mycobacteria?
The ability of the immune system to mount an efficient immune response
to pathogens depends, among others, on its capacity to establish and
maintain a functional and diverse repertoire of T lymphocytes. T
lymphocytes differentiate within the thymus, in a complex process that
depends on three key features: thymic structure, antigens encountered
within the thymus and the milieu surrounding the differentiating cells. The thymus is extremely active and
establishes a diverse repertoire of T cells quite early in life, which suggested a role for the thymus mostly during
infancy. It is now clear, however, that the process of T cell differentiation and export to peripheral organs is
important also during adulthood. Of interest, the thymus was, for long, considered somehow protected from
infection, or at least, not clearly affected by infection.
We and others have recently shown that infection influences T cell differentiation, either directly or indirectly
(through systemic increase in the levels of corticosteroids and of pro-inflammatory cytokines), which opens new
questions on the role of the thymus throughout life. Of relevance in the context of infection by Mycobacteria, is
the alteration of thymic structure and function. Specifically, mycobacterial infections alter T cell differentiation,
which impacts on the ability of the host to fight against infection. Maintaining a functional thymic environment is
essential to maintain T cell differentiation and prevent the emergence of central tolerance to the invading
pathogens, which will be discussed.
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HARVARD MEDICAL SCHOOL - PORTUGAL PROGRAM // 4TH INTERNATIONAL SYMPOSIUM: IMMUNOMEDICINE
MEET THE SPEAKERS
lecture 3
NUNO ALVES
The Quest for the Thymus: Molecular and Cellular Mechanisms
Required for Thymus Development and Function
The production of T lymphocytes by the thymus, also known as
thymopoiesis, is not constant during life and deficits in thymic function
arise in several physiopathological settings ranging from aging to infection
and myeloablative conditioning regimens prior to allogeneic hematopoietic
transplantation. Thus, the development of approaches to regenerate thymic activity in disease is an emergent
clinical goal.
In the thymus, essentially all steps of thymopoiesis require interactions between T lymphocyte precursors
(thymocytes) and thymic epithelial cells (TECs). TECs are classically divided into two specialized subsets,
cortical (cTECs) and medullary (mTECs), which derived from a common bipotent epithelial progenitor. Whereas
cTECs are important at early stages of thymopoiesis, mTECs regulate later phases of T cell development. The
identification of thymic epithelial progenitor cells (TEPCs) has been a quest in the recent years given the
possibility of developing cell-based therapies to alter thymic function. Recent findings suggest that TEC
differentiation proceeds through compartment-specific progenitors for cTECs and mTECs, although the details
of precursor-progeny relationship are unresolved. The partitioning of TEPCs into cTECs and mTECs requires
reciprocal instructive signals from thymocytes, a symbiotic process known as “thymic crosstalk”. While the
molecular basis of mTEC maturation has been partially elucidated, our understanding about the differentiation
pathway of cTECs remains largely undisclosed.
I will discuss our recent findings on the cellular and molecular pathways involved in cTEC differentiation in
normal and pathological conditions. We aim to provide with a detailed framework for cTEC development and
function that may be integrated into therapeutics to improve thymic functioning in acquired and congenital
immunodeficiencies.
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HARVARD MEDICAL SCHOOL - PORTUGAL PROGRAM // 4TH INTERNATIONAL SYMPOSIUM: IMMUNOMEDICINE
MEET THE SPEAKERS
lecture 4
JONATHAN KAGAN
Innate Immunity from Insects to Man
I have been studying Pattern Recognition Receptor signaling pathways as
a means of understating the earliest events that initiate immunity to
infection. Our work initiated with studies of the Toll-like Receptor (TLR)
signaling networks, which mainly operate in professional phagocytes and
function to detect microorganisms that enter our bodies. The organizing
principles that govern TLR signaling are entirely unknown and their elucidation will likely reveal answers to
several fundamental questions that apply to the study of vaccine design. My research has focused primarily on
defining the subcellular sites of TLR signal transduction. We have established that TLR adaptor proteins
function as pairs of sorting and signaling adaptors, where the sorting adaptor functions to recruit the signaling
adaptor to a subcellular site that contains an activated TLR. Our work provided the first in vivo evidence that the
localization of these adaptor proteins in important for controlling microbial infections. In addition, we have
defined a new signal transduction pathway activated when mammalian cells are exposed to bacterial LPS. This
new pathway is most notable in that signal transduction is not initiated by the classic LPS receptor TLR4, but is
rather triggered by the LPS binding protein CD14. Upon encountering LPS, CD14 triggers a signaling response
that internalizes TLR4 into endosomes, where the classic TRIF-mediated signaling events that lead to interferon
expression are activated. These studies provide the first evidence that TLR4 does not control all cellular
responses to bacterial LPS, an observation that may have broad implications for the understanding of signal
transduction in general.
Recently, we have extended our work to the cytosolic pattern recognition receptors of the RIG-I like receptor
(RLR) family, which functions in all mammalian cells to detect viral infections. Using a similar logic that we have
applied to the TLR network, we have discovered a new subcellular site of antiviral signal transduction. In
addition to the previously described mitochondria, RLR signaling also occurs from peroxisomes, an organelle
never before implicated in innate immunity. This work has allowed a new area of my research to emerge, and
we will focus on extending our initial studies of the RLR signaling network to further define the role of
peroxisomes in antiviral immunity.
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HARVARD MEDICAL SCHOOL - PORTUGAL PROGRAM // 4TH INTERNATIONAL SYMPOSIUM: IMMUNOMEDICINE
MEET THE SPEAKERS
lecture 5
BRUNO SILVA-SANTOS
T cells in cancer and autoimmunity
T lymphocytes are critically involved in both preventing and causing
pathology. Whereas they play protective roles against infectious
microrganisms and tumors, they can be highly pathogenic in
autoimmunity and chronic inflammatory diseases. For example, T cells
producing interleukin-17 (T17) are required to fight bacterial and fungal
infections, but they are also major drivers of type 1 diabetes, multiple sclerosis and psoriasis. Moreover, recent
data has highlighted a diversity of T cell subsets that can be involved in such processes, often playing
antagonistic roles.
For instance, the pro-inflammatory action of T17 cells is counteracted by the anti-inflammatory function of
regulatory T (Treg) cells. In my laboratory we investigate the molecular mechanisms underlying the
differentiation and activation of key T cell subsets. We have identified various new molecular players, such as
the tumor necrosis factor superfamily member CD70 and its receptor CD27, which promote Treg development
while inhibiting T17 differentiation and function. This makes CD70/ CD27 a promising candidate pathway for
intervention in autoimmunity and chronic inflammation.
On the other hand, we also study T cell responses to tumors, and have dissected the molecular mechanisms of
tumor cell recognition by gamma-delta T cells, a highly cytotoxic T cell subset that is being evaluated in cancer
clinical trials. We have identified the Natural Killer receptors NKG2D and NKp30 as major determinants of
leukemia/ lymphoma targeting by human gamma-delta T cells. We are now building on these findings toward
the development of novel immunotherapy protocols against cancer.
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HARVARD MEDICAL SCHOOL - PORTUGAL PROGRAM // 4TH INTERNATIONAL SYMPOSIUM: IMMUNOMEDICINE
MEET THE SPEAKERS
lecture 6
MARGARIDA SOUTO-CARNEIRO
B is for Bad: Altered B cell response in primary Immunodeficiencies
and Neurodegeneration
B lymphocytes and plasma cells play a central role in the immune
response both as regulators (cytokine production; antigen presentation;
cell-cell interaction) and as antibody-producing cells. Dramatic functional
alterations in peripheral blood B lymphocytes subsets are a hallmark of
chronic inflammatory diseases, in particular those with an autoimmune basis. In chronic autoimmune
inflammation B cells exhibit abnormal proliferation, maturation and apoptosis, and produce antibodies against
self-antigens, which enter the antigen processing pathway after pathogenic tissue and/or cell destruction. The
precise mechanisms underlying this auto-reactivity are still ill understood. We will discuss two questions about
autoantibodies and abnormal B cell responses in contexts usually not associated with “classical” autoimmune
diseases:
1)
How do reactive oxygen species (ROS) control B cell tolerance, and prevent chronic inflammation? Using
a combination of human samples from patients with chronic granulomatous diseases –a primary
immunodeficiency- and the corresponding mouse model, we will debate how mutations in the NADPHoxidase complex and deficient production of ROS leads to autoantibody production through type I
Interferon pathway (even in germ-free conditions); how DSS-induced colitis is exacerbated; how the
development of memory B cells in a secondary immune response is impaired; and how the response to
Candida albicans is deficient.
2)
Is there evidence for chronic inflammation in neurodegeneration leading to movement impairment? Using
blood B cells from Parkinson’s Disease patients we study how B cell-derived regulatory T cell formation is
impaired and how the production of autoantibodies is increased, under conditions where B cell function
and intracellular signaling pathways are altered.
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HARVARD MEDICAL SCHOOL - PORTUGAL PROGRAM // 4TH INTERNATIONAL SYMPOSIUM: IMMUNOMEDICINE
MEET THE SPEAKERS
lecture 7
SUNG-YUN PAI
Translational Investigation in Congenital Immunodeficiency
The study of congenital disorders of the immune system have led to
seminal discoveries about the genes that control immune cell
development and function. A veritable explosion in gene discovery in this
field has led to the identification of ~150 genes that cause congenital
immunodeficiency in humans. Simultaneously, medical advances in the
treatment of these rare disorders has made allogeneic hematopoietic stem cell transplantation the standard
therapy and ultimately paved the way for the use of somatic gene therapy.
My laboratory focuses on translational investigations in congenital immunodeficiency and its treatment. We
gather samples from children with rare immunodeficiencies including severe combined immunodeficiency
(SCID), Wiskott-Aldrich syndrome and others, and investigate the effects of the various genes responsible and
specific mutations on immune development and function. We were involved in the development and
implementation of a universal newborn screening program to detect SCID in newborn dried blood spots at birth
and have uncovered interesting and unexpected phenotypes of SCID in the process. We are examining the
effect of different types of allogeneic transplantation methods on the immune reconstitution of SCID patients,
particularly with regards to B cell function and dysregulation. Finally, we are conducting gene therapy trials in
the X-linked form of SCID (due to mutations in IL2RG) and in Wiskott-Aldrich syndrome in collaboration with
colleagues in the US and Europe.
Through these investigations we aim to understand the mechanisms underlying these genetic disorders,
improve diagnostic techniques, and ultimately advance the field by improving outcomes of both standard and
experimental therapeutic approaches.
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HARVARD MEDICAL SCHOOL - PORTUGAL PROGRAM // 4TH INTERNATIONAL SYMPOSIUM: IMMUNOMEDICINE
ABOUT
HARVARD MEDICAL SCHOOL – PORTUGAL PROGRAM
The HMS-PT Program is a wide-ranging initiative, involving professors, researchers and students from all 8
schools of Medicine in Portugal, as well as the country's main biomedical research laboratories. It aims at
modernizing and improving the quality of medical education in Portugal, whilst also broadening the scope of
cooperation between Portuguese medical schools and associated laboratories in such a way as to spur the
creation of a truly competitive level of training at the international level.
The translational research activities are designed to help populate Portuguese research institutions with an
increasingly sophisticated clinical and translational research capacity, and to expand the rate and quality of
Portuguese clinical and translational research contributions to the international community. The program is also
designed to foster long-lasting collaborative ventures, both within Portugal and between Portuguese and
Harvard research groups.
COIMBRA AND UNIVERSITY OF COIMBRA
Sometimes referred to as a town of students, Coimbra is one of the three
main urban centres in Portugal. The town nowadays covers an area of
319,41 km², with a total population of about 144,000 people. The Mondego
river crosses through the city.
The richness of Coimbra rests mostly on the University of Coimbra, one of
the oldest in Europe, with about 20,000 students – the city has a total of
35,000 higher education students distributed across a multiplicity of
graduation courses, awarding all academic degrees in fields ranging from
medicine and biomedical sciences to aeronautical engineering and
mathematics.
THE VENUE
Auditório da Unidade Central da Faculdade de Medicina da Universidade de Coimbra
Unidade Central, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, Celas
CONTACTS
For more information please visit www.hmsportugal.pt
Please direct all further enquiries to [email protected]
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HARVARD MEDICAL SCHOOL - PORTUGAL PROGRAM // 4TH INTERNATIONAL SYMPOSIUM: IMMUNOMEDICINE