Sam Thiagalingam

Boston University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Hamid M. Abdolmaleky

Boston University

102

Panagiotis Papageorgis

European University Cyprus

Arthur W. Lambert

AstraZeneca (United States)

Sait Ozturk

Fırat University

Chen Khuan Wong

Boston University

Yuriy O. Alekseyev

Boston University

Björn M. Reinhard

Boston University

Adam C. Gower

Boston University

Rekha Raghunathan

Eli Lilly (United States)

Arunthathi Thiagalingam

Boston University

Cooperative Institutions

Boston University

Johns Hopkins University

Harvard University

Johns Hopkins Medicine

Howard Hughes Medical Institute

Icahn School of Medicine at Mount Sinai

Massachusetts General Hospital

Case Western Reserve University

Iran University of Medical Sciences

University of Pennsylvania

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Data from Tumor Cell-Derived Periostin Regulates Cytokines That Maintain Breast Cancer Stem Cells

Arthur W. Lambert Chen Khuan Wong Sait Ozturk Panagiotis Papageorgis Rekha Raghunathan

<div>AbstractBasal-like breast cancer (BLBC) is an aggressive subtype of breast cancer which is often enriched with cancer stem cells (CSC), but the underlying molecular basis for this connection remains elusive. We hypothesized that BLBC cells are able to establish a niche permissive to the maintenance of CSCs and found that tumor cell-derived periostin (POSTN), a component of the extracellular matrix, as well as a corresponding cognate receptor, integrin αvβ3, are highly expressed in a subset of BLBC cell lines as well as in CSC-enriched populations. Furthermore, we demonstrated that an intact periostin–integrin β3 signaling axis is required for the maintenance of breast CSCs. POSTN activates the ERK signaling pathway and regulates NF-κB–mediated transcription of key cytokines, namely IL6 and IL8, which in turn control downstream activation of STAT3. In summary, these findings suggest that BLBC cells have an innate ability to establish a microenvironmental niche supportive of CSCs.Implications: The findings reported here indicate that POSTN produced by CSCs acts to reinforce the stem cell state through the activation of integrin receptors and the production of key cytokines. Mol Cancer Res; 14(1); 103–13. ©2015 AACR.</div>

Periostin

10.1158/1541-7786.c.6539814.v1

Cite

Citations (0)

Maternal Gut Microbiome-Mediated Epigenetic Modifications in Cognitive Development and Impairments: A New Frontier for Therapeutic Innovation

Nutrients (2024)

Shabnam Nohesara Hamid M. Abdolmaleky Faith Dickerson Adrian A. Pinto‐Tomás Dilip V. Jeste

Cognitive impairment in various mental illnesses, particularly neuropsychiatric disorders, has adverse functional and clinical consequences. While genetic mutations and epigenetic dysregulations of several genes during embryonic and adult periods are linked to cognitive impairment in mental disorders, the composition and diversity of resident bacteria in the gastrointestinal tract—shaped by environmental factors—also influence the brain epigenome, affecting behavior and cognitive functions. Accordingly, many recent studies have provided evidence that human gut microbiota may offer a potential avenue for improving cognitive deficits. In this review, we provide an overview of the relationship between cognitive impairment, alterations in the gut microbiome, and epigenetic alterations during embryonic and adult periods. We examine how various factors beyond genetics—such as lifestyle, age, and maternal diet—impact the composition, diversity, and epigenetic functionality of the gut microbiome, consequently influencing cognitive performance. Additionally, we explore the potential of maternal gut microbiome signatures and epigenetic biomarkers for predicting cognitive impairment risk in older adults. This article also explores the potential roles of nutritional deficiencies in programming cognitive disorders during the perinatal period in offspring, as well as the promise of gut microbiome-targeted therapeutics with epigenetic effects to prevent or alleviate cognitive dysfunctions in infants, middle-aged adults, and older adults. Unsolved challenges of gut microbiome-targeted therapeutics in mitigating cognitive dysfunctions for translation into clinical practice are discussed, lastly.

Epigenome

Cognitive Decline

10.3390/nu16244355

Cite

Citations (1)

Supplementary methods and figure legends from Targeting RICTOR Sensitizes SMAD4-Negative Colon Cancer to Irinotecan

Chen Khuan Wong Arthur W. Lambert Sait Ozturk Panagiotis Papageorgis Delia Lopez

Supplementary methods and figure legends

10.1158/1541-7786.22514461.v1

Cite

Citations (0)

Oncogenic forms of p53 inhibit p53-regulated gene expression

Science (1992)

S E Kern JA Pietenpol Sam Thiagalingam A. E. Seymour Kenneth W. Kinzler

Mutant forms of the gene encoding the tumor suppressor p53 are found in numerous human malignancies, but the physiologic function of p53 and the effects of mutations on this function are unknown. The p53 protein binds DNA in a sequence-specific manner and thus may regulate gene transcription. Cotransfection experiments showed that wild-type p53 activated the expression of genes adjacent to a p53 DNA binding site. The level of activation correlated with DNA binding in vitro. Oncogenic forms of p53 lost this activity. Moreover, all mutants inhibited the activity of coexpressed wild-type p53, providing a basis for the selection of such mutants during tumorigenesis.

Transcription

10.1126/science.1589764

Cite

Citations (933)

Supplementary Table 4 from Smad Signaling Is Required to Maintain Epigenetic Silencing during Breast Cancer Progression

Panagiotis Papageorgis Arthur W. Lambert Sait Ozturk Fangming Gao Hongjie Pan

Supplementary Table 4 from Smad Signaling Is Required to Maintain Epigenetic Silencing during Breast Cancer Progression

Table (database)

Tumor progression

10.1158/0008-5472.22386389.v1

Cite

Citations (0)

Supplementary Figure S1-S10 from Targeting RICTOR Sensitizes SMAD4-Negative Colon Cancer to Irinotecan

Chen Khuan Wong Arthur W. Lambert Sait Ozturk Panagiotis Papageorgis Delia Lopez

S1: SMAD4+/+ and SMAD4-/- colon cancer cells were serum-starved and seeded on transwells and allowed to cross the membrane for 24 hours (transwell migration; RFU, relative fluorescence unit; mean {plus minus} SD, n = 3 biological replicates; **P < 0.01). S2: RICTOR depletion in SMAD4-negative colon cancer cells using shRNA#2 was measured by RT-qPCR (RT-qPCR; mean {plus minus} SD, n = 3 technical replicates; ***P < 0.001). B, Western blotting shows the relative levels of RICTOR, p-AKTS473, and cleaved-caspase 3 upon knockdown of RICTOR and in response to irinotecan. C, The indicated cell lines were treated with irinotecan (10μM) for 72 hours. S3: Cells depleted of RICTOR were serum starved and seeded on transwells and allowed to cross the membrane for 24 hours (transwell migration; RFU, relative fluorescence unit; mean {plus minus} SD, n = 6 biological replicates; ***P < 0.001). S4: A, Western blot shows the relative levels of RICTOR and p-AKTS47 in SW403 cells upon transfection with the indicated siRNAs. B, siRNA-transfected SW403 cells were treated with irinotecan (10μM) for 120 hours. Viability of cells was normalized to DMSO-treated controls (cell viability assay; mean {plus minus} SD, n = 3 biological replicates; **P < 0.01). S5: High RICTOR/AKT1 expression correlates with worse survival in colon cancer. S6: Targeting AKT with MK2206 sensitizes SMAD4-negative SW403 colon cancer cells to irinotecan. S7: Targeting AKT with either AKTi-1/2 or MK2206 sensitizes SMAD4-negative colon cancer cells to irinotecan. S8: No toxicity observed in mice exposed to MK2206 and irinotecan. S9: Targeting AKT with MK2206 sensitizes SMAD4-negative ASPC1 and CFPAC1 pancreatic cancer cells to irinotecan. S10: In silico Kaplan-Meier analyses showing the correlation between SMAD4, RICTOR, or AKT1 expression and overall survival (OS) in pancreatic cancer patients.

Viability assay

10.1158/1541-7786.22514467

Cite

Citations (0)

Supplementary Fig. S1 from Tumor Cell-Derived Periostin Regulates Cytokines That Maintain Breast Cancer Stem Cells

Arthur W. Lambert Chen Khuan Wong Sait Ozturk Panagiotis Papageorgis Rekha Raghunathan

POSTN Expression if TGF-beta-dependent in M cells

Periostin

Breast tumor

10.1158/1541-7786.22511040

Cite

Citations (0)

Metastic Progression of Breast Cancer by Allelic Loss on Chromosome 18q21

Sam Thiagalingam

10.21236/ada450548

Cite

Citations (0)

hBub1 deficiency triggers a novel p53 mediated early apoptotic checkpoint pathway in mitotic spindle damaged cells

Cancer Biology & Therapy (2009)

Fangming Gao Jose F. Ponte Mary Levy Panagiotis Papageorgis Sait Öztürk

It has been universally believed that spindle assembly checkpoint (SAC) proteins which include the kinetochore proteins are involved in monitoring the faithful segregation of sister chromatids during cell division and hence defects in these proteins result in anueploidy. Furthermore, there are multiple sources of experimental data to suggest that a defect in p53 could also promote genomic instability leading to anueploidy. Despite these observations, a molecular basis for the prevention of aneuploidy to maintain genomic integrity upon activation of SAC has largely remained elusive. In this report, we demonstrate a novel mechanism for the maintenance of a balance between cell survival and apoptosis upon activation of SAC. We found that depletion of the outer kinetochore protein hBub1 upon activation of SAC primarily triggers early cell death mediated by p53. This phenomenon is further supported by the up-regulation of p53 down-stream pro-apoptotic genes, BAX and PUMA as well as a corresponding increase in the cleavage products of PARP and caspase 3, markers of apoptosis upon depletion of hBub1 in SAC activated cells. On the other hand, as expected, concomitant loss of both hBub1 and p53 resulted in disabling of the p53 mediated cell death pathway leading to the accumulation of cells with aneuploidy/polyploidy.Commentary also to:hBub1 negatively regulates p53 mediated early cell death upon mitotic checkpoint activationFangming Gao, Jose F Ponte, Panagiotis Papageorgis, Mary Levy, Sait Ozturk, Arthur W. Lambert, Arunthathi Thiagalingam, Hamid Mostafavi Abdolmaleky, Beth A Sullivan and Sam Thiagalingam

Spindle checkpoint

Mitotic catastrophe

Chromosome instability

10.4161/cbt.8.7.7928

Cite

Citations (12)

Reduced Risk of Cancer in Schizophrenia, a Bridge Toward Etio-Pathology and Therapy of Both Diseases

Springer eBooks (2015)

Mohammad Reza Eskandari Hamid M. Abdolmaleky Jin‐Rong Zhou Sam Thiagalingam

Cancer Therapy

Bridge (graph theory)

10.1007/978-94-017-9639-2_5

Cite

Citations (1)