Valentina Serra
Technologist
Area of interest:
Valentina Serra, biologist, obtained her PhD in Medical Genetics, Metabolic Diseases and Nutrigenomics at the University of Sassari in 2016, under the supervision of Prof. Francesco Cucca, with a thesis entitled “Study of the effect of cigarette smoking on the immune system in the population of Ogliastra”. She has been a CNR technologist since 2022 and works at the IRGB in Lanusei. Since 2012 she has been collaborating in the ProgeNIA project, where she is mainly involved in the study of the human immune system using flow cytometry. Specifically, Valentina is involved in measuring hundreds of immune cell populations circulating in peripheral blood and studying their functionality using activation and suppression assays. The aim of her research is to
-Understand how genetics and environmental factors, such as cigarette smoke or infections, regulate the architecture and functionality of the immune system;
-Identify biological links between immune cells and disease
-Identify potential therapeutic targets for targeted pharmacological intervention.
Most significant publications:
2024
Örr`u, Valeria; Serra, Valentina; Marongiu, Michele; Lai, Sandra; Lodde, Valeria; Zoledziewska, Magdalena; Steri, Maristella; Loizedda, Annalisa; Lobina, Monia; Piras, Maria Grazia; Virdis, Francesca; Delogu, Giuseppe; Marini, Maria Giuseppina; Mingoia, Maura; Floris, Matteo; Masala, Marco; Castelli, M Paola; Mostallino, Rafaela; Frau, Jessica; Lorefice, Lorena; Farina, Gabriele; Fronza, Marzia; Carmagnini, Daniele; Carta, Elisa; Pilotto, Silvy; Chessa, Paola; Devoto, Marcella; Castiglia, Paolo; Solla, Paolo; Zarbo, Roberto Ignazio; Idda, Maria Laura; Pitzalis, Maristella; Cocco, Eleonora; Fiorillo, Edoardo; Cucca, Francesco"
Implications of disease-modifying therapies for multiple sclerosis on immune cells and response to COVID-19 vaccination Journal Article
In: Front. Immunol., 15 , pp. 1416464, 2024.
@article{Orru2024-hd,
title = {Implications of disease-modifying therapies for multiple sclerosis on immune cells and response to COVID-19 vaccination},
author = {Valeria Örr`u and Valentina Serra and Michele Marongiu and Sandra Lai and Valeria Lodde and Magdalena Zoledziewska and Maristella Steri and Annalisa Loizedda and Monia Lobina and Maria Grazia Piras and Francesca Virdis and Giuseppe Delogu and Maria Giuseppina Marini and Maura Mingoia and Matteo Floris and Marco Masala and M Paola Castelli and Rafaela Mostallino and Jessica Frau and Lorena Lorefice and Gabriele Farina and Marzia Fronza and Daniele Carmagnini and Elisa Carta and Silvy Pilotto and Paola Chessa and Marcella Devoto and Paolo Castiglia and Paolo Solla and Roberto Ignazio Zarbo and Maria Laura Idda and Maristella Pitzalis and Eleonora Cocco and Edoardo Fiorillo and Francesco" Cucca},
doi = {10.3389/fimmu.2024.1416464},
year = {2024},
date = {2024-07-01},
urldate = {2024-07-01},
journal = {Front. Immunol.},
volume = {15},
pages = {1416464},
publisher = {Frontiers Media SA},
abstract = {Introduction: Disease-modifying therapies (DMTs) have been shown
to improve disease outcomes in multiple sclerosis (MS) patients.
They may also impair the immune response to vaccines, including
the SARS-CoV-2 vaccine. However, available data on both the
intrinsic immune effects of DMTs and their influence on cellular
response to the SARS-CoV-2 vaccine are still incomplete.
Methods: Here, we evaluated the immune cell effects of 3 DMTs on
the response to mRNA SARS-CoV-2 vaccination by comparing MS
patients treated with one specific therapy (fingolimod, dimethyl
fumarate, or natalizumab) with both healthy controls and
untreated patients. We profiled 23 B-cell traits, 57 T-cell
traits, and 10 cytokines, both at basal level and after
stimulation with a pool of SARS-CoV-2 spike peptides, in 79 MS
patients, treated with DMTs or untreated, and 32 healthy
controls. Measurements were made before vaccination and at three
time points after immunization. Results and Discussion: MS
patients treated with fingolimod showed the strongest immune
cell dysregulation characterized by a reduction in all measured
lymphocyte cell classes; the patients also had increased immune
cell activation at baseline, accompanied by reduced specific
immune cell response to the SARS-CoV-2 vaccine. Also, anti-spike
specific B cells progressively increased over the three time
points after vaccination, even when antibodies measured from the
same samples instead showed a decline. Our findings demonstrate
that repeated booster vaccinations in MS patients are crucial to
overcoming the immune cell impairment caused by DMTs and
achieving an immune response to the SARS-CoV-2 vaccine
comparable to that of healthy controls.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Introduction: Disease-modifying therapies (DMTs) have been shown
to improve disease outcomes in multiple sclerosis (MS) patients.
They may also impair the immune response to vaccines, including
the SARS-CoV-2 vaccine. However, available data on both the
intrinsic immune effects of DMTs and their influence on cellular
response to the SARS-CoV-2 vaccine are still incomplete.
Methods: Here, we evaluated the immune cell effects of 3 DMTs on
the response to mRNA SARS-CoV-2 vaccination by comparing MS
patients treated with one specific therapy (fingolimod, dimethyl
fumarate, or natalizumab) with both healthy controls and
untreated patients. We profiled 23 B-cell traits, 57 T-cell
traits, and 10 cytokines, both at basal level and after
stimulation with a pool of SARS-CoV-2 spike peptides, in 79 MS
patients, treated with DMTs or untreated, and 32 healthy
controls. Measurements were made before vaccination and at three
time points after immunization. Results and Discussion: MS
patients treated with fingolimod showed the strongest immune
cell dysregulation characterized by a reduction in all measured
lymphocyte cell classes; the patients also had increased immune
cell activation at baseline, accompanied by reduced specific
immune cell response to the SARS-CoV-2 vaccine. Also, anti-spike
specific B cells progressively increased over the three time
points after vaccination, even when antibodies measured from the
same samples instead showed a decline. Our findings demonstrate
that repeated booster vaccinations in MS patients are crucial to
overcoming the immune cell impairment caused by DMTs and
achieving an immune response to the SARS-CoV-2 vaccine
comparable to that of healthy controls.
to improve disease outcomes in multiple sclerosis (MS) patients.
They may also impair the immune response to vaccines, including
the SARS-CoV-2 vaccine. However, available data on both the
intrinsic immune effects of DMTs and their influence on cellular
response to the SARS-CoV-2 vaccine are still incomplete.
Methods: Here, we evaluated the immune cell effects of 3 DMTs on
the response to mRNA SARS-CoV-2 vaccination by comparing MS
patients treated with one specific therapy (fingolimod, dimethyl
fumarate, or natalizumab) with both healthy controls and
untreated patients. We profiled 23 B-cell traits, 57 T-cell
traits, and 10 cytokines, both at basal level and after
stimulation with a pool of SARS-CoV-2 spike peptides, in 79 MS
patients, treated with DMTs or untreated, and 32 healthy
controls. Measurements were made before vaccination and at three
time points after immunization. Results and Discussion: MS
patients treated with fingolimod showed the strongest immune
cell dysregulation characterized by a reduction in all measured
lymphocyte cell classes; the patients also had increased immune
cell activation at baseline, accompanied by reduced specific
immune cell response to the SARS-CoV-2 vaccine. Also, anti-spike
specific B cells progressively increased over the three time
points after vaccination, even when antibodies measured from the
same samples instead showed a decline. Our findings demonstrate
that repeated booster vaccinations in MS patients are crucial to
overcoming the immune cell impairment caused by DMTs and
achieving an immune response to the SARS-CoV-2 vaccine
comparable to that of healthy controls.
2022
Serra, Valentina; Fiorillo, Edoardo; Cucca, Francesco; Orr`u, Valeria
Quantifying the detrimental effects of multiple freeze/thaw cycles on primary human lymphocyte survival and function Journal Article
In: Int. J. Mol. Sci., 24 (1), pp. 634, 2022.
@article{Serra2022-xa,
title = {Quantifying the detrimental effects of multiple freeze/thaw cycles on primary human lymphocyte survival and function},
author = {Valentina Serra and Edoardo Fiorillo and Francesco Cucca and Valeria Orr`u},
doi = {10.3390/ijms24010634.},
year = {2022},
date = {2022-12-01},
urldate = {2022-12-01},
journal = {Int. J. Mol. Sci.},
volume = {24},
number = {1},
pages = {634},
publisher = {MDPI AG},
abstract = {The use of cryopreserved peripheral blood mononuclear cells is
common in biological research. It is widely accepted that
primary cells are rendered unusable by several freezing cycles,
although this practice might be very helpful when the biological
material is valuable and its re-collection is impractical. To
determine the extent to which primary cells undergoing repeated
freezing cycles are comparable to one another and to fresh
samples, we evaluated overall lymphocyte viability, their
proliferation and cytokine production capabilities, as well as
the levels of 27 cell subtypes in ten human peripheral blood
mononuclear cells frozen for five years and repeatedly thawed.
As expected, we observed a progressive increase in cell death
percentages on three rounds of thawing, but the frequency of the
main lymphocyte subsets was stable across the three thawings.
Nevertheless, we observed a significant reduction of B cell
frequency in frozen samples compared to fresh ones. On repeated
thawings and subsequent conventional stimulation, lymphocyte
proliferation significantly decreased, and IL-10, IL-6, GM-CSF,
IFN-gamma, and IL-8 showed a trend to lower values.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The use of cryopreserved peripheral blood mononuclear cells is
common in biological research. It is widely accepted that
primary cells are rendered unusable by several freezing cycles,
although this practice might be very helpful when the biological
material is valuable and its re-collection is impractical. To
determine the extent to which primary cells undergoing repeated
freezing cycles are comparable to one another and to fresh
samples, we evaluated overall lymphocyte viability, their
proliferation and cytokine production capabilities, as well as
the levels of 27 cell subtypes in ten human peripheral blood
mononuclear cells frozen for five years and repeatedly thawed.
As expected, we observed a progressive increase in cell death
percentages on three rounds of thawing, but the frequency of the
main lymphocyte subsets was stable across the three thawings.
Nevertheless, we observed a significant reduction of B cell
frequency in frozen samples compared to fresh ones. On repeated
thawings and subsequent conventional stimulation, lymphocyte
proliferation significantly decreased, and IL-10, IL-6, GM-CSF,
IFN-gamma, and IL-8 showed a trend to lower values.
common in biological research. It is widely accepted that
primary cells are rendered unusable by several freezing cycles,
although this practice might be very helpful when the biological
material is valuable and its re-collection is impractical. To
determine the extent to which primary cells undergoing repeated
freezing cycles are comparable to one another and to fresh
samples, we evaluated overall lymphocyte viability, their
proliferation and cytokine production capabilities, as well as
the levels of 27 cell subtypes in ten human peripheral blood
mononuclear cells frozen for five years and repeatedly thawed.
As expected, we observed a progressive increase in cell death
percentages on three rounds of thawing, but the frequency of the
main lymphocyte subsets was stable across the three thawings.
Nevertheless, we observed a significant reduction of B cell
frequency in frozen samples compared to fresh ones. On repeated
thawings and subsequent conventional stimulation, lymphocyte
proliferation significantly decreased, and IL-10, IL-6, GM-CSF,
IFN-gamma, and IL-8 showed a trend to lower values.
Serra, Valentina; Orr`u, Valeria; Lai, Sandra; Lobina, Monia; Steri, Maristella; Cucca, Francesco; Fiorillo, Edoardo
Comparison of whole blood cryopreservation methods for extensive flow cytometry immunophenotyping Journal Article
In: Cells, 11 (9), pp. 1527, 2022.
@article{Serra2022-nw,
title = {Comparison of whole blood cryopreservation methods for extensive flow cytometry immunophenotyping},
author = {Valentina Serra and Valeria Orr`u and Sandra Lai and Monia Lobina and Maristella Steri and Francesco Cucca and Edoardo Fiorillo},
doi = {10.3390/cells11091527},
year = {2022},
date = {2022-05-01},
urldate = {2022-05-01},
journal = {Cells},
volume = {11},
number = {9},
pages = {1527},
publisher = {MDPI AG},
abstract = {Fresh blood immunophenotyping by flow cytometry, based on the
reliable simultaneous detection of several markers in a cell, is
the method of choice to study the circulating human immune
system. Especially in large and multicenter studies, high sample
quality is difficult to achieve, and adequate collection and
storage of samples with fine-tuned whole blood cryopreservation
is mandatory. Here, we compared the quality of immunophenotypic
data obtained from fresh blood with those obtained after five
cryopreservation methods by quantifying the levels of 41 immune
cell populations. They comprised B and T lymphocyte subsets and
their maturation stages, as well as monocytes and granulocytes.
Three methods used fixative solutions and two other methods used
dimethyl sulfoxide solutions to preserve cell viability. The
fixative methods prevented detection of markers critical for
identification of B and T cell subsets, including CD27, CXCR3,
and CCR6. The other two methods permitted reliable
discrimination of most immune-cell populations in thawed
samples, though some cell frequencies varied compared to the
corresponding fresh sample. Of those two methods, the one
preserving blood in media containing dimethyl sulfoxide produced
results that were most similar to those with fresh samples.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Fresh blood immunophenotyping by flow cytometry, based on the
reliable simultaneous detection of several markers in a cell, is
the method of choice to study the circulating human immune
system. Especially in large and multicenter studies, high sample
quality is difficult to achieve, and adequate collection and
storage of samples with fine-tuned whole blood cryopreservation
is mandatory. Here, we compared the quality of immunophenotypic
data obtained from fresh blood with those obtained after five
cryopreservation methods by quantifying the levels of 41 immune
cell populations. They comprised B and T lymphocyte subsets and
their maturation stages, as well as monocytes and granulocytes.
Three methods used fixative solutions and two other methods used
dimethyl sulfoxide solutions to preserve cell viability. The
fixative methods prevented detection of markers critical for
identification of B and T cell subsets, including CD27, CXCR3,
and CCR6. The other two methods permitted reliable
discrimination of most immune-cell populations in thawed
samples, though some cell frequencies varied compared to the
corresponding fresh sample. Of those two methods, the one
preserving blood in media containing dimethyl sulfoxide produced
results that were most similar to those with fresh samples.
reliable simultaneous detection of several markers in a cell, is
the method of choice to study the circulating human immune
system. Especially in large and multicenter studies, high sample
quality is difficult to achieve, and adequate collection and
storage of samples with fine-tuned whole blood cryopreservation
is mandatory. Here, we compared the quality of immunophenotypic
data obtained from fresh blood with those obtained after five
cryopreservation methods by quantifying the levels of 41 immune
cell populations. They comprised B and T lymphocyte subsets and
their maturation stages, as well as monocytes and granulocytes.
Three methods used fixative solutions and two other methods used
dimethyl sulfoxide solutions to preserve cell viability. The
fixative methods prevented detection of markers critical for
identification of B and T cell subsets, including CD27, CXCR3,
and CCR6. The other two methods permitted reliable
discrimination of most immune-cell populations in thawed
samples, though some cell frequencies varied compared to the
corresponding fresh sample. Of those two methods, the one
preserving blood in media containing dimethyl sulfoxide produced
results that were most similar to those with fresh samples.
Serra, Valentina; Orr`u, Valeria; Steri, Maristella; Fiorillo, Edoardo; Cucca, Francesco; Zoledziewska, Magdalena
Genetic variant within CDK6 regulates immune response to palbociclib treatment Journal Article
In: Clin. Immunol., 235 (108777), pp. 108777, 2022.
@article{Serra2022-br,
title = {Genetic variant within CDK6 regulates immune response to palbociclib treatment},
author = {Valentina Serra and Valeria Orr`u and Maristella Steri and Edoardo Fiorillo and Francesco Cucca and Magdalena Zoledziewska},
doi = {10.1016/j.clim.2021.108777},
year = {2022},
date = {2022-02-01},
urldate = {2022-02-01},
journal = {Clin. Immunol.},
volume = {235},
number = {108777},
pages = {108777},
publisher = {Elsevier BV},
abstract = {Everyone carries a set of genetic variants that contribute to
regulation of the levels of blood cells, with unknown clinical
impact. One of them, rs445 within the cell-cycle checkpoint gene
CDK6, reduces the levels of myeloid cell types including
granulocytes. We treated CD3+ T cells and whole blood with
palbociclib in 41 individuals, who were stratified by genotype
for analyses. In T cells we assessed cell cycle and apoptosis,
whereas in whole blood, apoptosis in activated (CD11b+),
unactivated (CD11b-) granulocytes, cytotoxic (CD8 + CD4-), and
helper (CD8-CD4+) T cells. We find that rs445 modulates the
immune response of CD8+ T cells. It also increases the level of
apoptotic CD11b + activated granulocytes after palbociclib
treatment, which, in synergy with neutropenia, may affect drug
related adverse events. These results suggest that the effect of
palbociclib treatment may depend on underlying genetically
encoded individual immune response as well as the direct
response to the drug.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Everyone carries a set of genetic variants that contribute to
regulation of the levels of blood cells, with unknown clinical
impact. One of them, rs445 within the cell-cycle checkpoint gene
CDK6, reduces the levels of myeloid cell types including
granulocytes. We treated CD3+ T cells and whole blood with
palbociclib in 41 individuals, who were stratified by genotype
for analyses. In T cells we assessed cell cycle and apoptosis,
whereas in whole blood, apoptosis in activated (CD11b+),
unactivated (CD11b-) granulocytes, cytotoxic (CD8 + CD4-), and
helper (CD8-CD4+) T cells. We find that rs445 modulates the
immune response of CD8+ T cells. It also increases the level of
apoptotic CD11b + activated granulocytes after palbociclib
treatment, which, in synergy with neutropenia, may affect drug
related adverse events. These results suggest that the effect of
palbociclib treatment may depend on underlying genetically
encoded individual immune response as well as the direct
response to the drug.
regulation of the levels of blood cells, with unknown clinical
impact. One of them, rs445 within the cell-cycle checkpoint gene
CDK6, reduces the levels of myeloid cell types including
granulocytes. We treated CD3+ T cells and whole blood with
palbociclib in 41 individuals, who were stratified by genotype
for analyses. In T cells we assessed cell cycle and apoptosis,
whereas in whole blood, apoptosis in activated (CD11b+),
unactivated (CD11b-) granulocytes, cytotoxic (CD8 + CD4-), and
helper (CD8-CD4+) T cells. We find that rs445 modulates the
immune response of CD8+ T cells. It also increases the level of
apoptotic CD11b + activated granulocytes after palbociclib
treatment, which, in synergy with neutropenia, may affect drug
related adverse events. These results suggest that the effect of
palbociclib treatment may depend on underlying genetically
encoded individual immune response as well as the direct
response to the drug.
2020
Orrù, V; Steri, M; Sidore, C; Marongiu, M; Serra, V; Olla, S; Sole, G; Lai, S; Dei, M; Mulas, A; Virdis, F; Piras, MG; Lobina, M; Marongiu, M; Pitzalis, M; Deidda, F; Loizedda, A; Onano, S; Zoledziewska, M; Sawcer, S; Devoto, M; Gorospe, M; Abecasis, GR; Floris, M; Pala, M; Schlessinger, D; Fiorillo, E; Cucca, F
Complex genetic signatures in immune cells underlie autoimmunity and inform therapy Journal Article
In: Nat Genet, 52 (10), pp. 1036–1045, 2020.
@article{pmid32929287,
title = {Complex genetic signatures in immune cells underlie autoimmunity and inform therapy},
author = {V Orrù and M Steri and C Sidore and M Marongiu and V Serra and S Olla and G Sole and S Lai and M Dei and A Mulas and F Virdis and MG Piras and M Lobina and M Marongiu and M Pitzalis and F Deidda and A Loizedda and S Onano and M Zoledziewska and S Sawcer and M Devoto and M Gorospe and GR Abecasis and M Floris and M Pala and D Schlessinger and E Fiorillo and F Cucca},
doi = {10.1038/s41588-020-0684-4},
year = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Nat Genet},
volume = {52},
number = {10},
pages = {1036--1045},
abstract = {We report on the influence of ~22 million variants on 731 immune cell traits in a cohort of 3,757 Sardinians. We detected 122 significant (P < 1.28 × 10-11) independent association signals for 459 cell traits at 70 loci (53 of them novel) identifying several molecules and mechanisms involved in cell regulation. Furthermore, 53 signals at 36 loci overlapped with previously reported disease-associated signals, predominantly for autoimmune disorders, highlighting intermediate phenotypes in pathogenesis. Collectively, our findings illustrate complex genetic regulation of immune cells with highly selective effects on autoimmune disease risk at the cell-subtype level. These results identify drug-targetable pathways informing the design of more specific treatments for autoimmune diseases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We report on the influence of ~22 million variants on 731 immune cell traits in a cohort of 3,757 Sardinians. We detected 122 significant (P < 1.28 × 10-11) independent association signals for 459 cell traits at 70 loci (53 of them novel) identifying several molecules and mechanisms involved in cell regulation. Furthermore, 53 signals at 36 loci overlapped with previously reported disease-associated signals, predominantly for autoimmune disorders, highlighting intermediate phenotypes in pathogenesis. Collectively, our findings illustrate complex genetic regulation of immune cells with highly selective effects on autoimmune disease risk at the cell-subtype level. These results identify drug-targetable pathways informing the design of more specific treatments for autoimmune diseases.
- Lanusei
- 0782 480674