About

Aristidis Floratos, PhD, is an assistant professor in the Department of Biomedical Informatics and the executive research director at the Center for Computational Biology and Bioinformatics at Columbia University Vagelos College of Physicians and Surgeons. His lab develops collaborative bioinformatics software to support the analysis and visualization of genomic data from various domains, including gene expression, sequence, protein structure, and systems biology. This software leverages standards-based middleware technologies to provide seamless access to remote data, annotation, and computational servers, enabling researchers with limited local resources to benefit from public infrastructure. The Floratos Lab is also focused on developing innovative, systems biology-driven methodologies that improve the detection of low-risk genetic factors contributing to drug-induced serious adverse events (SAEs). In collaboration with an international network of investigators, the lab leads the analysis of genome-wide genotyping and exome sequencing data for drug-induced disorders such as serious skin rash, liver injury, cardiac arrhythmias, and osteonecrosis of the jaw. Additionally, the lab has developed motif discovery algorithms used to study the evolutionary architecture of genomic sequences.

Research topics

• Biology
• Internal medicine
• Medicine
• Computer Science
• Cancer research
• Immunology
• Data science
• Computational biology

Selected publications

• The CALERIE™ Genomic Data Resource

  bioRxiv (Cold Spring Harbor Laboratory) · 2024 · 3 citations

  • Computer Science
  • Computer Science
  • Data science

  - the first ever randomized, controlled trial of long-term CR in healthy, non-obese humans - broadly supports a similar pattern of effects in humans. To expand our understanding of the molecular pathways and biological processes underpinning CR effects in humans, we generated a series of genomic datasets from stored biospecimens collected from n=218 participants during the trial. These data constitute the first publicly-accessible genomic data resource for a randomized controlled trial of an intervention targeting the biology of aging. Datasets include whole-genome SNP genotypes, and three-timepoint-longitudinal DNA methylation, mRNA, and small RNA datasets generated from blood, skeletal muscle, and adipose tissue samples (total sample n=2327). The CALERIE Genomic Data Resource described in this article is available from the Aging Research Biobank. This mult-itissue, multi-omic, longitudinal data resource has great potential to advance translational geroscience.

  PublisherOA PDFDOI

• Abstract B059: A novel pancreatic cancer mouse model with human immunity

  Cancer Research · 2024

  • Cancer research
  • Medicine
  • Immunology

  Abstract The iRGD tumor-penetrating peptide delivers chemically linked drugs and even co-injected free drugs selectively to extravascular tumor tissue by targeting the αvβ5 integrin and neuropilin-1 (NRP1). A phase 1b clinical trial showed that iRGD appears to safely double the response rate of standard chemotherapy in patients with stage 4 pancreatic ductal adenocarcinoma (PDAC). We recently found that long-term iRGD treatment, even as a monotherapy, reduced regulatory T cells (Tregs) selectively in the PDAC tissue, which led to the expansion of CD8+ T cells and improved efficacy of immunotherapy in syngeneic PDAC mice. This finding led to the discovery of αvβ5 integrin being a novel targetable marker for tumor-resident Tregs in PDAC mice. Our recent data show that αvβ5 integrin+ Tregs are also present in human PDAC tissue. To study the significance of αvβ5 integrin+ human Tregs as a therapeutic target for iRGD, we developed a humanized PDAC (huPDAC) mouse model by transplanting human PDAC cells into human immune system (HIS) mice, which harbor fully matured human CD8+ and CD4+ T cells, natural killer T cells, B cells, and dendritic cells. The CD8+ T cells are human leukocyte antigen (HLA)-restricted and show a tumor antigen-specific response. We orthotopically implanted HLA-matched human PDAC cells into HLA-A2-positive HIS mice. Both an established human PDAC cell line (PANC-1) and patient-derived PDAC cells (0779E) successfully formed orthotopic tumors and liver metastases. The tumors were infiltrated by various human immune cells at a ratio similar to that found in patient-derived PDAC tissues. Of note, αvβ5 integrin+ human Tregs were also noted in the tumors but not in the spleen. iRGD monotherapy increased the ratio of CD8+ T cells per Tregs in the tumors, suggesting that iRGD will likely function as an immunomodulator in humans. The first patient was recently dosed in a new phase 1b/2a clinical trial (iLSTA Trial: ACTRN12623000223639), which assesses the safety and preliminary efficacy of iRGD in combination with standard-of-care chemotherapy and immunotherapy in locally advanced PDAC patients. Citation Format: Norio Miyamura, Kodai Suzuki, Richard A. Friedman, Aristidis Floratos, Yuki Kunisada, Kazuya Masuda, Andrew M. Lowy, Moriya Tsuji, Kazuki N. Sugahara. A novel pancreatic cancer mouse model with human immunity [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B059.

  PublisherDOI

• A pancreatic cancer mouse model with human immunity

  bioRxiv (Cold Spring Harbor Laboratory) · 2023 · 2 citations

  • Medicine
  • Cancer research
  • Biology

  Pancreatic ductal adenocarcinoma (PDAC) is characterized by a tumor immune microenvironment (TIME) that promotes resistance to immunotherapy. A preclinical model system that facilitates studies of the TIME and its impact on the responsiveness of human PDAC to immunotherapies remains an unmet need. We report a novel mouse model, which develops metastatic human PDAC that becomes infiltrated by human immune cells recapitulating the TIME of human PDAC. The model may serve as a versatile platform to study the nature of human PDAC TIME and its response to various treatments.

  PublisherOA PDFDOI

• ILT3.Fc–CD166 Interaction Induces Inactivation of p70 S6 Kinase and Inhibits Tumor Cell Growth

  The Journal of Immunology · 2017-12-20 · 48 citations

  article

  Abstract The blockade of immune checkpoints by anti-receptor and/or anti-ligand mAb is one of the most promising approaches to cancer immunotherapy. The interaction between Ig-like transcript 3 (ILT3), a marker of tolerogenic dendritic cells, also known as LILRB4/LIR5/CD85k, and its still unidentified ligand on the surface of activated human T cells is potentially important for immune checkpoint blockade. To identify the ILT3 ligand, we generated mAb by immunizing mice with Jurkat acute T cell leukemia, which binds ILT3.Fc to its membrane. Flow cytometry, mass spectrometry, and Biacore studies demonstrated that the ILT3 ligand is a CD166/activated leukocyte cell adhesion molecule. Knockdown of CD166 in primary human T cells by nucleofection abolished the capacity of ILT3.Fc to inhibit CD4+ Th cell proliferation and to induce the generation of CD8+CD28− T suppressor cells. CD166 displays strong heterophilic interaction with CD6 and weaker homophilic CD166–CD166 cell adhesion interaction. ILT3.Fc inhibited the growth of CD166+ tumor cell lines (TCL) derived from lymphoid malignancies in vitro and in vivo. CRISPR-Cas9–based knockout of CD166 from TCL abrogated ILT3.Fc binding and its tumor-inhibitory effect. The mechanism underlying the effect of ILT3.Fc on tumor cell growth involves inhibition of the p70S6K signaling pathway. Blockade of CD166 by ILT3.Fc inhibited progression of human TCL in NOD.Cg-Prkdc Il-2rg/SzJ mice, suggesting its potential immunotherapeutic value.

  PublisherDOI

• Pattern discovery in biology: theory and applications

  1999-01-01 · 5 citations

  articleSenior author
  Publisher

Frequent coauthors

• Richard A. Friedman

  Columbia University Irving Medical Center

  3 shared

• Kazuya Masuda

  Columbia University

  3 shared

• Moriya Tsuji

  Columbia University

  3 shared

• Kazuki N. Sugahara

  Columbia University Irving Medical Center

  2 shared

• Calen P. Ryan

  Columbia University

  2 shared

• Luigi Ferrucci

  Institute on Aging

  2 shared

• Kodai Suzuki

  Nagaoka University of Technology

  2 shared

• Andrew M. Lowy

  2 shared