Translational Immunology

Project title

“Cellular immune responses against human cancer”

Academic Board Contact PersonEnrico Lugli, enrico.lugli@humanitasresearch.it
Laboratory name: Lab of Translational Immunology

Abstract

We use high-content single cell approaches including single cell RNA sequencing and 30-parameter polychromatic flow cytometry and bioinformatics to dissect the diversity of the human T cell compartment in the circulation and in tissues, with the final aim of identifying the most potent T cell subsets to be used in adoptive cell transfer approaches for the treatment of human cancer. We further characterize these T cell subsets at the molecular level and test them in xenogeneic models at the preclinical level. We next evaluate their presence of in individuals with cancer and test their relevance in the anti-tumor immune response or during the course of immunotherapeutic treatments.

Molecular Cardiology

3 Projects are associated to Molecular Cardiology:

  1. “Involvement of miRNAs in the cross-talk between immune and vascular cells in the accelerated onset of atherosclerosis induced by diabetes”
  2. Epigenetics of cardiovascular diseases; molecular mechanisms of heart failure
  3. “The interplay between cellular aging and immune response in human colorectal liver metastasis: senescence as a new prognostic marker?”

 

1. Project title

“Involvement of miRNAs in the cross-talk between immune and vascular cells in the accelerated onset of atherosclerosis induced by diabetes”

Tutor / academic Board Contact Person: Leonardo Elia, Prof. Gianluigi Condorelli, gianluigi.condorelli@hunimed.eu

Laboratory name: Inflammation and Immunology in Cardiovascular Pathologies

Abstract

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia. The main causes of death and disability in diabetic people are vascular diseases. In those patients the incidence of atherosclerosis-induced cardiovascular diseases are 2 to 8-fold higher than in those without diabetes and the underlying molecular mechanisms are not well known. In vessels cellular cross-talk is a complex process and essential for the correct tissue response to pathological insults.

2. Main fields of interest

Epigenetics of cardiovascular diseases; molecular mechanisms of heart failure

Academic Board Contact Person: Prof. Gianluigi Condorelli, gianluigi.condorelli@hunimed.eu
Laboratory name: Molecular Cardiology

Abstract

The molecular bases of heart failure are characterized by significant modifications of gene expression profiles of cells composing the myocardium. Regulatory networks governing gene expression in cardiomyocytes, the contractile cellular unit of the heart, are under intense investigation, not least because dysregulation of the gene programme has a fundamental role in the development of a failing myocardium. Epigenetic modifications and functional non-protein-coding RNAs (ncRNAs) are important contributors to this process. The epigenetic modifications that regulate transcription comprise post-translational changes to histones—the proteins around which DNA is wound—as well as modifications to cytosine residues on DNA.

3. Project title

“The interplay between cellular aging and immune response in human colorectal liver metastasis: senescence as a new prognostic marker?”

Tutor / Academic Board Contact Person: Francesca Faggioli, Prof. Gianluigi Condorelli, gianluigi.condorelli@hunimed.eu
Laboratory name: Inflammation and Immunology in Cardiovascular Pathologies

Abstract

Colorectal liver metastases (CLM) are the third leading cause of cancer death in the world. Liver resection combined with chemotherapy remains the only curative treatment for the disease. Standard chemotherapy has the potential to induce accelerated aging in cells, a phenomenon herein referred as cellular senescence. Cells cease to proliferate, resulting in tumor regression. 

Laboratory of Leukocyte Biology

Project title

“Chemokine receptor targeting to harness neutrophil anti-tumor immune responses”

Academic Board Contact Person: Prof. Bonecchi, raffaella.bonecchi@hunimed.eu
Laboratory name: Laboratory of Leukocyte Biology

Abstract

The project will study the role of chemokine receptors in the anti-tumor immune response of neutrophils. Neutrophils, essential to protect the host during infections, are also able to exert tumor suppressive effects controlling cancer progression but are often subverted in their functions by tumor microenvironment. It is emerging that neutrophils are a heterogeneous population and that they have different functions in tumors depending on their differentiation and activation state.

Hepatobiliary Immunopathology

Project title

“Cholangiocytes-on-a-chip: a platform to identify medical therapy for cholangiocarcinoma”

Tutor / Academic Board Contact Person: Ana Lleo, prof. Guido Torzilliguido.torzilli@hunimed.eu
Laboratory name: Hepatobiliary Immunopathology, Humanitas Research Hospital

Abstract

Cholangiocarcinoma (CCA) is a deadly cancer of the biliary epithelium. Incidence and mortality rates are currently increasing, and pharmacological therapies are generally unsuccessful. Thus, there is an obvious need for better understanding tumor pathogenesis and eventually tailoring effective therapies. Target cells are cholangiocytes (BECs), a heterogeneous population of epithelial cells, however, the intratumoral infiltrate of CCA patients impacts prognosis after complete resection. Due to the complexity of the in vivo cellular interactions, these mechanisms and metabolic activation pathways are largely unknown.

Transcriptional and epigenetic control

2 Projects are associated to the Laboratory of Transcriptional and epigenetic control:

  1. “Spatial transcriptomics in human pancreatic cancer”
  2. “Understanding metabolic regulation of the inflammatory gene expression program”

 

1. Project title

“Spatial transcriptomics in human pancreatic cancer”

Academic Board Contact Person: Prof. Gioacchino Natoli, gioacchino.natoli@hunimed.eu

Abstract

Pancreatic ductal adenocarcinoma cells infiltrate nerves in 100% of cases, even at early stages of the disease. PDAC cells generating infiltrates under the epineurium appear to consist mainly of a differentiated population. Understanding the identity and properties of these cells, including the expression of the cell autonomous inflammatory program discussed above, will likely provide critical information on how to therapeutically target them.
To characterize the PDAC cells that invade large nerves we will use a panel of complementary approaches.

2. Project title

“Understanding metabolic regulation of the inflammatory gene expression program”

Academic Board Contact Person: Prof. Gioacchino Natoli, gioacchino.natoli@hunimed.eu

Abstract

Inflammatory responses require rapid changes in gene expression in myeloid cells. A critical issue relates to the interplay between transcriptional and metabolic changes determined by macrophage activation. Gene expression and metabolic states are coordinately controlled. First, activation-driven metabolic changes activation are determined by transcriptional changes. Second, many metabolic intermediates are cofactors of chromatin-modifying enzymes.

Mucosal immunology and microbiota

2 Projects are associated to the Mucosal immunology and microbiota Unit:

  1. “Analysis of the role of the microbiota in tumor metastatization”
  2. “Analysis of the role of the microbiota in evasion of cancer immunotherapy strategies”

 

1. Project title

“Analysis of the role of the microbiota in tumor metastatization”

Academic Board Contact Personprof. Maria Rescignomaria.rescigno@hunimed.eu

Abstract

We have recently demonstrated the existence of a vascular barrier in the intestine that controls what enters the portal circulation and reaches the liver. We have hypothesized that this barrier is a gateway for tumor metastatization. In this project, we want to assess what is the role of the microboita in opening the barrier and favouring tumor spreading.

Main technical approaches

2. Project title

“Analysis of the role of the microbiota in evasion of cancer immunotherapy strategies”

Academic Board Contact Personprof. Maria Rescignomaria.rescigno@hunimed.eu

Abstract

We have recently demonstrated the existence of e new mechanism of action of the anti-proliferative antibody Cetuzimab which is mediated by the immune system. We found a similar activity also associated to Trastuzumab and have identified a protein which is found overrepresented in sera of patients that do not respond to therapy. In this project we want to assess better the function of this protein, as well as if its expression is regulated by the microbiota.

Main technical approaches

Cardio Center

Project title

“Coronary artery disease progression in patients with acute coronary syndromes and diabetes mellitus”

Academic Board Contact Person: Dr. Stefanini, giulio.stefanini@hunimed.eu

Laboratory name: Cardio Center, Humanitas Research Hospital

Abstract

100 patients with ACS will be included (50 patients with and 50 patients without DM, matched by age and gender). Patients will undergo percutaneous revascularization of the infarct-related vessel with implantation of a fully bioresorbable scaffold, and will undergo 18FNaF PET-coronary CT after 2 days. At 12 months, 18FNaF PET-coronary CT will be repeated to quantify neointimal suppression at the site of bioresorbable scaffold implantation and to characterize CAD progression (burden and activity) in non-infarct related vessels. Samples for metabolomics, miRNAs and inflammation analyses will be collected at baseline and 12 months.

Synaptic development

Project title

“Essential Circuits and Neurons that underlie distinctive symptoms in autism spectrum disorders”

Academic Board Contact Person: Carlo Sala

Laboratory name: Physiological and pathological mechanisms of synaptic development, CNR Neuroscience Institute

Abstract

Autism spectrum disorders (ASDs) are defined as neurodevelopmental diseases that are presenting with 2 main symptoms: impaired social interaction and stereotypic repetitive behavior. 1% of ASD cases (prevalence: 1 in 16.000) are due to mutations of SHANK genes. The Shank proteins are a family of scaffolding proteins of the postsynaptic density of excitatory synapses that serve as “master organizer” of postsynaptic protein complexes. 

Neuro Center

Project title

“Mitophagy and autophagy as a new target to promote neuroprotection”

Academic Board Contact Person: Prof. Matteolimichela.matteoli@hunimed.eu
Laboratory name: Neuro Center, Humanitas

Abstract

Brain ischemia is the 3rd cause of death in people over 65, worldwide. It has no effective treatments beside recanalization strategies that cannot be always usefully applied. To minimize disability, it is crucial to identify alternative early, effective and long lasting pharmacological interventions. Autophagy and mitophagy are potential therapeutic targets in neurodegenerative conditions such as brain ischemia. In the stroked brain, enhanced autophagy induces neuronal death in the ischemic penumbra while increased mitophagy exerts protective effects. 

Experimental Immunopathology

Project title

“Development of a novel checkpoint molecule of lymphoid cells in cancer”

Academic Board Contact Person: Prof. Garlanda, cecilia.garlanda@hunimed.eu
Laboratory name: Laboratory of Experimental Immunopathology, Humanitas Research Hospital

Abstract

IL-1R8 is a member of the IL-1 receptor family with negative regulatory functions. Recently it has been observed that in Natural Killer cells IL-1R8 acts as a checkpoint and that its genetic deletion increases the maturation and functional activities of NK cells towards tumors, metastases and viral infections. The aim of the project is to extend the knowledge on the role of IL-1R8 in the functional activity of lymphocytes and to develop the inhibition of this molecule as a therapeutic target in preclinical cancer models.

Institute of Neuroscience, CNR and Laboratory of Pharmacology and Brain Pathology

Project title

“Role of the SNARE protein, SNAP25, in aging”

Academic Board Contact Person: Elisabetta Menna
Laboratory name: Institute of Neuroscience, CNR and Laboratory of Pharmacology and Brain Pathology, Fondazione Humanitas per la Ricerca

Abstract

Aging is characterized by alterations in muscle catabolism that can result in sarcopenia, a condition that anticipates frailty. The etiology of sarcopenia is multifactorial, but research has been mainly focused on muscular factors even though a neurological origin could be postulated. Neuromuscular junctions (NMJs) have the characteristic structural features of other chemical synapses and act as interface between the nervous and skeletal muscular systems, playing a crucial role in the age-related musculoskeletal impairment. 

Medical Genetics and RNA Biology

2 Projects are associated to the Laboratory of Medical Genetics and RNA Biology:

  1. “Small molecules modulating splicing as novel CFTR amplifier drugs”
  2. “Study of altered splicing and backsplicing processes as predisposing contributors to Multiple Sclerosis”

 

1. Project title

“Small molecules modulating splicing as novel CFTR amplifier drugs”

Academic Board Contact Person: Prof. Stefano Duga, stefano.duga@hunimed.eu

Abstract

The high frequency of cystic fibrosis (CF) suggests that reduced CFTR function was evolutionarily advantageous. Evidence that CFTR splicing is inefficient suggests that also high levels of missplicing could have been selected explaining the high frequency (up to 5%) of some variants known to modulate CFTR splicing, such as the TGmTn polymorphism. Incorrectly-processed CFTR mRNAs may represent an endogenous reservoir for additional CFTR synthesis, provided that the splicing defect is corrected.

2. Project title

“Study of altered splicing and backsplicing processes as predisposing contributors to Multiple Sclerosis”

Academic Board Contact Personprof. Rosanna Asseltarosanna.asselta@hunimed.eu

Abstract

Alternative splicing (AS) is a post-transcriptional mechanism expanding the information content of the transcriptome through the expression of multiple mRNAs from individual genes. AS regulation involves cis-acting elements, trans-acting factors, and novel players such as circular RNAs (circRNAs, the products of spliceosomal backsplicing, BS) and long noncoding RNAs (lncRNAs). Accumulating data –and our preliminary results– suggest that altered RNA processing is linked to Multiple Sclerosis (MS).

Diagnostic Imaging and Radiotherapy

Project title

“Development and validation of Advanced Image Analysis for medical applications”

Academic Board Contact PersonProf. Arturo Chiti, arturo.chiti@hunimed.eu
Laboratory name: Diagnostic Imaging and Radiotherapy 

Abstract

The success of precision medicine is largely dependent on robust quantitative biomarkers. In recent years the role of medical imaging is evolving. Images can be used to extrapolate predictive and prognostic information that may be used to tailor patient management.
In the last years different, from the methodological point of view, approaches for medical image analysis have emerged, radiomics and machine learning techniques, including the convolutional neural networks (CNNs).

Applied Physics, Biophysics and Microfluidics

Project title

“Assessing the role of the microenvironment in cell migration”

Academic Board Contact Person: prof. Roberto Rusconiroberto.rusconi@hunimed.eu 
Laboratory name: Applied Physics, Biophysics and Microfluidics Lab

Abstract

Cell migration plays a central role in a wide variety of biological phenomena, ranging from gastrulation to development of the nervous system. In the inflammatory response, for example, leukocytes immigrate into areas of insult, where they mediate phagocytic and immune functions. Although the basic molecular mechanisms underlying cell migration are now fairly well characterized, their global integration and coordination at the cell scale are not fully understood, and motile phenotypes can vary significantly between types of cells and microenvironments. 

Experimental Cancer Therapeutics

Project title

“Optimizing the management of lymphoma patients in the era of precision medicine: using the liquid biopsy for disease outcome prediction and monitoring by circulating tumor DNA genotyping”

Academic Board Contact Person: prof. Carmelo Carlo Stella, carmelo.carlostella@hunimed.eu
Laboratory name: Experimental Cancer Therapeutics

Abstract

Although potentially curable, ~40% of diffuse large B-cell lymphoma (DLBCL), as well as ~25% of classical Hodgkin lymphoma (cHL) are not cured by front-line therapy. The optimal strategy for predicting outcome and monitoring response to therapy is not yet available. While imaging represents a surrogate of the presence of tumor cells, the availability of molecular markers of disease would allow a more accurate detection of residual lymphoma cells during treatment and follow-up. We will perform a prospective observational study in DLBCL and cHL patients receiving front-line therapy to validate analysis of circulating tumor DNA (ctDNA) as a novel approach to predict disease outcome and monitor minimal residual disease (MRD). In relapsed/refractory cHL patients receving checkpoint blockade therapy, ctDNA will be profiled to evaluate disease eradication and identify treatment-emergent mutations associated with therapy resistance.

Why
Humanitas
University?
An Established Institution

An Established Institution
Humanitas is a renowned healthcare institution that has offered Medical Degrees for well over a decade as a partner of the University of Milan.

An International Career

An International Career
Join our international medical community where classes are taught in English by experienced professors and medical doctors from around the world. Your degree will allow you to work as a MD in the EU and abroad.

Clinical Experience

Clinical Experience
Direct clinical experience is supported by a solid tutoring system and starts in your third year, which gives you considerable practical experience.

Innovative and Active Teaching

Innovative and Active Teaching
Humanitas curriculum is enhanced by a wide variety of active learning methods based on a student-centred approach (Problem-Based Learning, Case method, Concept maps, Simulated patients).

Milano and Italy

Milano and Italy
Enjoy the style, culture, gastronomy and entertainment of one of Europe's most exciting cities. Venture further to experience the delights of Italy or use the opportunity to learn Italian.

Advanced Research and Technology

Advanced Research and Technology
Humanitas can count on state-of-the-art technologies and research experience. A new simulation centre of 1000 sm, designed according to the highest technological standards, will be ready for autumn 2017.

Contact Us

Contact
Humanitas University
Via Rita Levi Montalcini 4,
Pieve Emanuele 20090 Milan, Italy

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From the highway

Go straight on from Porta Ticinese, to Corso San Gottardo, to via Meda, via Montegani, and via dei Missaglia, then follow the signs for Istituto Clinico Humanitas, or Basiglio Milano 3.

By public transport

Go straight on from Porta Ticinese, to Corso San Gottardo, to via Meda, via Montegani, and via dei Missaglia, then follow the signs for Istituto Clinico Humanitas, or Basiglio Milano 3.