Charlotte Kuperwasser

• PhD
• Director at Tufts University

A growing number of peer-reviewed publications have reported diverse cancer types appearing in temporal association with COVID-19 vaccination or infection. To characterize the nature and scope of these reports, a systematic literature search from January 2020 to October 2025 was conducted based on specified eligibility criteria. A total of 69 publi...

A growing number of peer-reviewed publications have reported diverse cancer types appearing in temporal association with COVID-19 vaccination or infection. To characterize the nature and scope of these reports, a systematic literature search from January 2020 to October 2025 was conducted based on specified eligibility criteria. A total of 69 publi...

Breast cancer etiology traditionally emphasizes genetic mutations, hormonal dynamics, and tissue aging. However, recent decades have seen a steady rise in breast cancer with a growing proportion of these tumors exhibiting estrogen receptor–positive (ER + ) phenotypes along with an alarming rise in early-onset breast cancer occurring in individuals...

Current breast organoid models, primarily based on self-assembly, face limitations in accurately mimicking the complex stages of tissue development, notably in replicating detailed tissue architectures and cellular diversity. Here, we demonstrate that a solitary human breast stem cell can, within a controlled hydrogel extracellular matrix environme...

The tumor microenvironment in triple-negative breast cancer (TNBC) is characterized by increased sensory nerve density, which contributes to cancer progression by promoting migration and metastasis. However, the origin of tumor-innervating nerves and the mechanisms driving sensory innervation into tumors remain poorly understood. Using in vivo retr...

In vitro tumor models are essential tools for cancer research, offering key insights into not only tumor biology but also therapeutic responses. The transition from traditional two-dimensional to three-dimensional organoid systems marks a paradigm shift in cancer modeling. Although two-dimensional models have been instrumental in elucidating fundam...

Understanding epithelial stem cell differentiation and morphogenesis during breast tissue development is essential, as disruption in these processes underlie breast cancer formation. We used a next-generation single-cell-derived organoid model to investigate how individual stem cells give rise to complex tissue. We show that discoidin domain recept...

Mesenchymal-epithelial interactions are well-established for organogenesis, but the role of immune cells in these processes remains less explored. Organoids offer powerful models for studying tissue development, especially where in vivo models are limited. In this study, we established an immune-epithelial co-culture model using an advanced 3D hydr...

Background/Objectives: The NavDx+Gyn blood test detects and quantifies fourteen HPV types in various sample types to provide a reliable means of detecting and monitoring HPV-driven gynecologic cancers. NavDx+Gyn is an extension of the NavDx assay, which identifies five high-risk HPV types. NavDx has been clinically validated in multiple independent...

Organoids have emerged as a powerful tool for modeling tissue growth and diseases. In this study, we introduce a groundbreaking organotypic culture technique that replicates the morphology, scale, and heterogeneity of human breast tissue, and includes a mesenchymal-like stromal component. A standout feature of this approach is the use of long-term...

The human breast is complex and comprised of multi-lineage and multi-structural elements. Recent work has shown that epithelial stem and progenitor cells use the collagen receptor Discoidin Domain Receptor 1 (DDR1) for differentiation into both basal and luminal cell lineages, which together are necessary for both ductal and alveolar morphogenesis....

Background Recent trials suggest that programmed cell death 1 (PD-1)-directed immunotherapy may be beneficial for some patients with anal squamous cell carcinoma and biomarkers predictive of response are greatly needed. Methods This multicenter phase II clinical trial ( NCT02919969 ) enrolled patients with metastatic or locally advanced incurable...

The varying pathways of mammary gland development across species and evolutionary history are underexplored, largely due to a lack of model systems. Recent progress in organoid technology holds the promise of enabling in-depth studies of the developmental adaptations that have occurred throughout the evolution of different species, fostering benefi...

Objectives: While survival outcomes are favorable for Human Papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCCs), early diagnosis may minimize treatment-related morbidity and mortality. This study evaluated circulating tumor tissue-modified viral (TTMV)-HPV DNA plasma testing to facilitate early diagnosis of HPV-positive OP...

Organoids have been widely used for studying tissue growth and modeling diseases, but achieving physiologically relevant architecture, size, and function has remained a challenge. Here, we develop a next-generation organotypic culture method that enables the formation of a highly patterned, complex, branched tissue that is spatially organized to ac...

Importance: Given the increased incidence of HPV-positive oropharyngeal carcinoma (OPC) in recent decades, identifying minimally invasive biomarkers for early diagnosis is essential to decreasing disease- and treatment-related morbidity. Two such biomarkers, circulating tumor HPV DNA (ctHPVDNA) and HPV16 E6 seropositivity, are highly sensitive and...

Introduction: Indeterminate results of clinical or imaging examinations are common across the care continuum, and decisions made can lead to overtreatment and psychological and financial harms for the patient. Additionally, due to the emergence of highly sensitive circulating tumor DNA assays, an indeterminate clinical status can also arise when mo...

Purpose Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease...

Fibroblasts are a major cell type within breast microenvironment which play key roles in tissue remodeling during the processes of normal development, injury, and malignancy. During wound healing and tumorigenesis, fibroblasts facilitate production and degradation of the extracellular matrix and produce inflammatory mediators which act as immune re...

The divergent events during mammary gland development between species and across evolution are not well studied mainly due to the lack of tractable model systems. In theory, advancements in the field of organoid technology now make it possible to study developmental processes adapted throughout species evolutions to accommodate advantageous phenoty...

Purpose: Despite favorable outcomes, up to 20% of patients with human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) will experience recurrence. Monitoring circulating tumor tissue modified viral (TTMV)-HPV DNA during post-treatment surveillance has emerged as a tool that has demonstrated >95% positive predictive value (P...

The transcription factor MYC is frequently altered in a large portion of human breast cancers; the gene is amplified in ~15% of breast cancers and overexpressed in another 30-50%. Mouse mammary tumor models driven by overexpression of MYC, such as MMTV-Myc, also exhibit a rapid onset and high frequency of mammary tumors indicating that MYC overexpr...

The NavDx® blood test analyzes tumor tissue modified viral (TTMV)-HPV DNA to provide a reliable means of detecting and monitoring HPV-driven cancers. The test has been clinically validated in a large number of independent studies and has been integrated into clinical practice by over 1000 healthcare providers at over 400 medical sites in the US. Th...

Purpose/Objective(s) We previously reported the results of a phase III clinical trial (MC1675) evaluating 30-36 Gy of adjuvant radiation therapy (RT) with weekly docetaxel (DART) vs standard of care (SOC) adjuvant (chemo)RT. We analyzed prospectively collected patient plasma specimens for circulating tumor tissue modified viral (TTMV)-HPV DNA as a...

6006 Background: NRG-HN002 was a phase II trial that randomized patients with p16-positive oropharynx cancer to 60 Gy IMRT with concurrent cisplatin (IMRT-C) or 60 Gy accelerated IMRT. The protocol specified plasma collection at pretreatment (t0), intratreatment (20-28 Gy, t1), and 2 weeks to 1 month posttreatment (t2); at these timepoints, TTMV wa...

Purpose Despite generally favorable outcomes, 15% to 25% of patients with human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) will have recurrence. Current posttreatment surveillance practices rely on physical examinations and imaging and are inconsistently applied. We assessed circulating tumor tissue modified viral (TT...

Purpose/Objective(s) Despite generally favorable outcomes, up to 20% of patients with human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) will experience recurrence within 5 years of curative-intent therapy; approximately half of recurrences present with distant disease. Current post-treatment surveillance practices rely...

Human papillomavirus (HPV), most commonly HPV16, causes a growing subset of head and neck squamous cell carcinomas (HNSCCs), including the overwhelming majority of oropharynx squamous cell carcinomas in many developed countries. Circulating biomarkers for HPV‐positive HNSCC may allow for earlier diagnosis, with potential to decrease morbidity and m...

Purpose A phase II multi-institutional clinical trial was conducted to determine overall survival (OS) in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with a combination of cetuximab and nivolumab. Patients and Methods Patients with R/M HNSCC were treated with cetuximab 500 mg/m² i.v. on day...

Background: Cancer-Associated Fibroblasts (CAFs) are a major cell type within breast tumor microenvironment (TME) which have emerged as a new target for cancer therapy given their contributions to tumor growth, metastasis, and suppression of the anti-tumor immune response. In the breast, CAFs are predominantly formed from conversion of tissue-resid...

Mammary morphogenesis is an orchestrated process involving differentiation, proliferation and organization of cells to form a bi-layered epithelial network of ducts and lobules embedded in stromal tissue. We have engineered a 3D biomimetic human breast that makes it possible to study how stem cell fate decisions translate to tissue-level structure...

Purpose/Objective(s) This study sought to measure circulating plasma tumor-tissue modified human papilloma virus DNA (TTMV-HPV DNA) and kinetics following trans-oral robotic surgery (TORS), neck dissection, and adjuvant (chemo)radiation for p16+ oropharyngeal squamous cell carcinoma (OPSCC). Materials/Methods Patients with p16+ OPSCC currently enr...

Cell fate decisions are critical for adequate tissue development, maintenance and regeneration. In the mammary gland, epithelial cell fates are tightly controlled by the microenvironment. Here, we review how cell fate decisions are regulated by components of the microenvironment during mammary gland development and how pathological changes in the m...

6063 Background: HPV genomic DNA in plasma and saliva has been widely studied, however more recently, circulating tumor human papillomavirus DNA (ctHPVDNA) has emerged as a reliable biomarker for surveillance in HPV+ oropharyngeal squamous cell carcinoma (OPSCC). A commercial assay for this biomarker distinguishes tumor-derived viral DNA (tumor-tis...

Selective pressure and signals from the tissue microenvironment drive metastasis and determine the survival of metastatic tumor cells at distant organs. Zhang et al. and Bado et al. apply CRISPR-mediated evolving barcode technology to elucidate the role of the bone microenvironment in the evolution of breast cancer metastasis.

The transcription factor Snai2, encoded by the SNAI2 gene, is an evolutionarily conserved C2H2 zinc finger protein that orchestrates biological processes critical to tissue development and tumorigenesis. Initially characterized as a prototypical epithelial-to-mesenchymal transition (EMT) transcription factor, Snai2 has been shown more recently to p...

Comprehensive sequencing approaches have allowed for the identification of the most frequent contributors to cancer, known as drivers. They have also revealed a class of mutations in understudied, infrequently altered genes, referred to as "long tail" (LT) drivers. A key challenge has been to find clinically relevant LT drivers and to understand ho...

DNA damage activates checkpoints that limit the replicative potential of stem cells, including differentiation. These checkpoints protect against cancer development but also promote tissue aging. Because mice lacking Slug/Snai2 exhibit limited stem cell activity, including luminobasal differentiation, and are protected from mammary cancer, we reaso...

Background: Increased transcription of the human endogenous retrovirus group HERV-K (HML-2) is often seen during disease. Although the mechanism of its tissue-specific activation is unclear, research shows that LTR CpG hypomethylation alone is not sufficient to induce its promoter activity and that the transcriptional milieu of a malignant cell co...

Our traditional understanding of phenotypic plasticity in adult somatic cells comprises dedifferentiation and transdifferentiation in the context of tissue regeneration or wound healing. Although dedifferentiation is central to tissue repair and stemness, this process inherently carries the risk of cancer initiation. Consequently, recent research s...

Background: Breast cancer is a heterogeneous disease encompassing multiple subtypes that differ in their molecular profiles, clinical course of progression, and response to therapeutics. Interestingly, breast cancers fall broadly into luminal and basal subtypes, which resemble the normal luminal and basal epithelial cells of the breast. This correl...

The epithelial compartment of the mammary gland contains basal and luminal cell lineages, as well as stem and progenitor cells that reside upstream in the differentiation hierarchy. Stem and progenitor cell differentiation is regulated to maintain adult tissue and mediate expansion during pregnancy and lactation. The genetic factors that regulate t...

In cancer, tumor suppressor genes (TSGs) are frequently truncated, causing their encoded products to be non-functional or dominant-negative. We previously showed that premature polyadenylation (pPA) of MAGI3 truncates the gene, switching its functional role from a TSG to a dominant-negative oncogene. Here we report that MAGI3 undergoes pPA at the i...

Increasing evidence suggests that repetitive elements may play a role in host gene regulation, particularly through the donation of alternative promoters, enhancers, splice sites, and termination signals. Elevated transcript expression of the endogenous retrovirus group HERV-K (HML-2) is seen in many human cancers, although the identity of the indi...

We have previously shown tumor suppressive effects of extracellular superoxide dismutase, EcSOD in breast cancer cells. In this study, an RTK signaling array revealed an inhibitory effect of EcSOD on c-Met phosphorylation and its downstream kinase c-Abl in MDA-MB231 cells. Moreover, an extracellular protein array showed that thrombospondin 1 (TSP-1...

Organogenesis and tissue development occur through sequential stepwise processes leading to increased lineage restriction and loss of pluripotency. An exception to this appears in the adult human breast, where rare variant epithelial cells exhibit pluripotency and multilineage differentiation potential when removed from the signals of their native...

Cleavage and polyadenylation is a fundamental process in the control of gene expression, yet how cancer cells deregulate this process to generate cancer-causing alterations is only beginning to be appreciated. We previously showed that in human breast cancer, premature polyadenylation of the tumor suppressor gene causes the expression of a truncate...

s: AACR Special Conference on DNA Repair: Tumor Development and Therapeutic Response; November 2-5, 2016; Montreal, QC, Canada The transcriptional repressor Slug/SNAI2 orchestrates epigenetic programs indispensable for tissue self-renewal and tumorigenesis. Although Slug-deficient animals are highly sensitive to lethal irradiation, the direct biol...

This abstract was withdrawn by the authors.

Luminal breast cancers are typically estrogen receptor–positive and generally have the best prognosis. However, a subset of luminal tumors, namely luminal B cancers, frequently metastasize and recur. Unfortunately, the causal events that drive their progression are unknown, and therefore it is difficult to identify individuals who are likely to rel...

Objectives: There is a lack of metrics that are representative of three-dimensional (3D) collagen fiber organization, despite the availability of high resolution 3D image stacks. This study aims to develop 3D orientation based biomarkers to quantify differences in the organization of collagen fibers between cancerous breast tissues and normal ones....

We develop 3D directional variance as a quantitative biomarker of truly 3D fibrillar organization, and establish its applications by characterizing collagen fibers and neuronal axons in the context of breast cancer and traumatic brain injury.

Overabundance of Slug protein is common in human cancer and represents an important determinant underlying the aggressiveness of basal-like breast cancer (BLBC). Despite its importance, this transcription factor is rarely mutated in BLBC, and the mechanism of its deregulation in cancer remains unknown. Here, we report that Slug undergoes acetylatio...

Top human PDZ domains predicted to bind the YAP PDZ-binding motif. DOI: http://dx.doi.org/10.7554/eLife.14730.017

Comprehensive list of candidate MAGI3-interacting proteins in MCF10A cells. DOI: http://dx.doi.org/10.7554/eLife.14730.016

Basal‐like breast cancer (BLBC) represents the most aggressive and deadliest breast cancer subtype, affecting 20% of breast cancer patients. Unlike other subtypes, few driver mutations have been identified and, thus, no targeted therapies have been established. We previously observed the transcriptional repressor Slug/ SNAI2 is frequently overexpre...

Over the past 20 years tremendous progress has been made in understanding the function of BRCA1 gene products. Yet one question still remains: why is mutation of BRCA1 typically associated with preferential development of breast and ovarian cancers and not tumors in other tissues? Here we discuss recent evidence documenting the effect of BRCA1-hapl...

The tumor microenvironment has complex effects in cancer pathophysiology that are not fully understood. Most cancer therapies are directed against malignant cells specifically, leaving pro-malignant signals from the microenvironment unaddressed. Defining specific mechanisms by which the tumor microenvironment contributes to breast cancer metastasis...

During the formation of breast cancer, many genes become altered as cells evolve progressively from normal to a pre-malignant to a malignant state of growth. How mutations in genes lead to specific subtypes of human breast cancer is only partially understood. Here we review how initial genetic or epigenetic alterations within mammary epithelial cel...

There is increasing appreciation that alterations to epigenetic mechanisms contribute directly to breast cancer development. In cancer cells, one such mechanism, called alternative polyadenylation (APA), has been observed to cause a general shortening of mRNA through the usage and premature cleavage of upstream poly(A) signals (PAS). However, while...

Obesity promotes breast cancer by enhancing the stiffness of breast adipose tissue through changes in the extracellular matrix (Seo et al., this issue). Copyright © 2015, American Association for the Advancement of Science.

The mammary gland undergoes dramatic post-natal growth beginning at puberty, followed by full development occurring during pregnancy and lactation. Following lactation, the alveoli undergo apoptosis, and the mammary gland reverses back to resemble the nonparous gland. This process of growth and regression occurs for multiple pregnancies, suggesting...

Although BRCA1 function is essential for maintaining genomic integrity in all cell types, it is unclear why increased risk of cancer in individuals harbouring deleterious mutations in BRCA1 is restricted to only a select few tissues. Here we show that human mammary epithelial cells (HMECs) from BRCA1-mutation carriers (BRCA1(mut/+)) exhibit increas...

The early diagnosis of cancers and continued monitoring of tumor growth would be greatly facilitated by the development of a blood-based, non-invasive, screening technique for early cancer detection. Current technologies for cancer screening and detection typically rely on imaging techniques or blood tests that are not accurate or sensitive enough...

Although mouse models have provided invaluable information on the mechanisms of mammary gland development, anatomical and developmental differences between human and mice limit full understanding of this fundamental process. Humanization of the mouse mammary gland by injecting immortalized human breast stromal cells into the cleared murine mammary...

Defining fiber orientation at each voxel within a 3D biomedical image stack is potentially useful for a variety of applications, including cancer, wound healing and tissue regeneration. Current methods are typically computationally intensive or inaccurate. Herein, we present a 3D weighted orientation vector summation algorithm, which is a generaliz...

Regulators of chromatin structure and gene expression contribute to tumor formation and progression. The co-repressor CoREST1 regulates the localization and activity of associated histone modifying enzymes including lysine specific demethylase 1 (LSD1) and histone deacetylase 1 (HDAC1). Although several CoREST1 associated proteins have been reporte...

How breast diversity is generated is a fascinating and fundamental question with important clinical implications. It is clear that the diversity of phenotypes displayed by breast cancer cells reflects the array of cell types present in the disease-free breast epithelium, including luminal, basal and stem cells. Therefore, it is hypothesized that th...

Background Although human breast development is mediated by hormonal and non-hormonal means, the mechanisms that regulate breast progenitor cell activity remain to be clarified. This limited understanding of breast progenitor cells has been due in part to the lack of appropriate model systems to detect and characterize their properties. Methods To...

Abstract SLUG, a member of the SNAIL family of transcriptional repressors, is known to play a diverse number of roles in the cell, and its deregulation has been observed in a variety of cancers including breast. Here, we focus on SLUG's role as a master regulator of mammary epithelial cell (MEC) fate and lineage commitment in the normal mammary gla...

IntroductionLineage tracing studies in mice have revealed the localization and existence of lineage-restricted mammary epithelial progenitor cells that functionally contribute to expansive growth during puberty and differentiation during pregnancy. However, extensive anatomical differences between mouse and human mammary tissues preclude the direct...

We have previously shown that silencing of the Rac exchange factor Tiam1 in tumor-associated fibroblasts induces increased invasion and metastasis in epithelial and cancer cells using 3D-tissue culture models and a mouse model of human breast cancer. Here we investigate the underlying mechanism using a novel method for isolating human breast cancer...

The JmjC domain histone H3K36me2/me1 demethylase NDY1/KDM2B is overexpressed in various types of cancer. Here we show that knocking down NDY1 in a set of 10 cell lines derived from a broad range of human tumors inhibited their anchorage-dependent and anchorage-independent growth by inducing senescence and/or apoptosis in some and by inhibiting G1 p...

Perturbations in stem cell activity and differentiation can lead to developmental defects and cancer. We use an approach involving a quantitative model of cell-state transitions in vitro to gain insights into how SLUG/SNAI2, a key developmental transcription factor, modulates mammary epithelial stem cell activity and differentiation in vivo. In the...

Lineage-committed cells of many tissues exhibit substantial plasticity in contexts such as wound healing and tumorigenesis, but the regulation of this process is not well understood. We identified the Hippo transducer WWTR1/TAZ in a screen of transcription factors that are able to prompt lineage switching of mammary epithelial cells. Forced express...

The prognosis of breast cancer is strongly influenced by the developmental stage of the breast when the tumor is diagnosed. Pregnancy-associated breast cancers (PABCs), cancers diagnosed during pregnancy, lactation, or in the first postpartum year, are typically found at an advanced stage, are more aggressive and have a poorer prognosis. Although t...

Obesity is one of the most important preventable causes of cancer and the most significant risk factor for breast cancer in postmenopausal women. Compared with lean women, obese women are more likely to be diagnosed with a larger, higher grade tumor, an increased incidence of lymph node metastases, and elevated risk of distant recurrence. However,...

RAS genes are commonly mutated in cancer; however, RAS mutations are rare in breast cancer, despite frequent hyperactivation of Ras and ERK. Here, we report that the RasGAP gene, RASAL2, functions as a tumor and metastasis suppressor. RASAL2 is mutated or suppressed in human breast cancer, and RASAL2 ablation promotes tumor growth, progression, and...

The characterization of cells with tumour initiating potential is significant for advancing our understanding of cancer and improving therapy. Aggressive, triple-negative breast cancers (TNBCs) are enriched for tumour-initiating cells (TICs). We investigated that hypothesis that VEGF receptors expressed on TNBC cells mediate autocrine signalling th...