About

Nadya Dimitrova, Ph.D., is an Associate Professor of Molecular, Cellular, and Developmental Biology at Yale University. Originally from Sofia, Bulgaria, she earned an Sc.B. in Biochemistry from Brown University in 2002 and completed her Ph.D. at Rockefeller University in 2009, where she studied the signaling and repair of dysfunctional telomeres in the laboratory of Dr. Titia de Lange. Her graduate work was recognized with the Harold M. Weintraub Graduate Student Award. As a postdoctoral fellow at MIT's Koch Institute for Integrative Cancer Research, she developed genetic mouse models to study the roles of noncoding RNAs in cancer biology. Her research focuses on understanding the functions and mechanisms of long noncoding RNAs in the context of cancer, aiming to deepen insights into their roles in regulating the cancer transcriptome and their importance for tumor initiation and progression. Her work has significant implications for understanding fundamental mechanisms underlying normal and cancer states and for developing RNA-based therapies in cancer. Nadya Dimitrova is a member of the Yale Center for RNA Science and Medicine and the Yale Cancer Center, and she teaches advanced undergraduate courses on Epigenetics and The Human Genome.

Research topics

• Biology
• Genetics
• Computational biology
• Medicine
• Cancer research
• Cell biology

Selected publications

• From evidence to action: the IARC’s role in strengthening cancer prevention and early detection

  JNCI Monographs · 2026-02-02

  article

  Prevention and early detection are central to reducing the global cancer burden, yet implementation remains uneven, particularly in low- and middle-income countries. This narrative review synthesizes the contributions of the International Agency for Research on Cancer (IARC) to translating evidence into policy and practice worldwide across vaccination, screening, and early diagnosis. Key advances include generating evidence that enabled the World Health Organization (WHO) recommendation of single-dose human papillomavirus vaccination; contributions to WHO Elimination of Cervical Cancer Initiative and Global Initiative on Breast Cancer; development of guidance for Helicobacter pylori screen-and-treat strategies; building decision platforms to optimize cost-effective strategies; and establishing CanScreen5 to benchmark cancer screening program performance globally. IARC led European Union screening status reports, codeveloped quality-assurance schemes, and standardized performance indicators. Through implementation research, capacity-building, and codesigned solutions, IARC supports prostate, gastric, and lung cancer screening pilots and equity-oriented approaches that strengthen health-care systems. By embedding evidence, modeling, and governance, IARC helps countries transition from pilots to population-level impact, accelerating progress toward WHO targets and equitable outcomes in cancer control.

  PublisherDOI

• Characterization of a Novel 53BP1-Dependent Mechanism that Promotes Non-Homologous End Joining of Deprotected Telomeres by Increasing Chromatin Mobility

  Digital Commons - RU (Rockefeller University) · 2025-09-08

  articleOpen access1st authorCorresponding

  When a double-stranded break (DSB) occurs in mammalian genomes, the local chromatin is altered through the modification of histones (notably the phosphorylation of H2AX) and the binding of DNA damage response factors (e.g. MDC1, 53BP1). Although several lines of evidence have pointed to a role for some of these factors in DSB repair through non-homologous end-joining (NHEJ), the mechanism of their contribution has not been established. To study the regulation of NHEJ, we have used as a model system dysfunctional telomeres, which are uncapped by the removal of the shelterin component, TRF2. As a consequence of TRF2 loss, deprotected chromosome ends trigger a sequence of events normally activated by the presence of DSBs. These include the instigation of ATM mediated activation of cell cycle checkpoints and the accumulation of DNA damage response factors at the telomeric chromatin. In addition, the NHEJ pathway repairs deprotected telomeres to generate chromosome end-to-end fusions. We have examined the roles of the Mre11/Rad50/NBS1 (MRN) complex, H2AX, MDC1, and 53BP1 in the NHEJ of dysfunctional telomeres. We have demonstrated that among these factors, 53BP1 is required for the fusion of telomeres, whereas the MRN complex, H2AX, and MDC1 only stimulate the efficiency of the repair process, most likely by mediating the recruitment of 53BP1 to uncapped chromosome ends. Furthermore, we have revealed the mechanism by which 53BP1 acts. We have shown that upon deprotection, telomeres become more dynamic and explore larger territories in a 53BP1-dependent manner. Faster mobility of DNA ends increases the chance that dysfunctional telomeres, which are uniformly scattered throughout the nucleus, will find one another and fuse. We have proposed that the dynamic behavior of DNA ends may be required to promote long-distance repair in general, and that it may play a role in other instances of NHEJ, such as during recombination in the immunoglobulin genes, where the DNA ends are initially at a distance. Furthermore, we have shown that the mechanism that promotes the mobility of uncapped chromosome ends requires microtubules. This finding suggests an unprecedented role for microtubules in the process of DNA repair in mammalian interphase cells. Moreover, it points to the existence of a trans-nuclear envelope bridge between damaged chromatin and cytoplasmic microtubules. Accordingly, our data indicate that mobility depends on the acetylation status of chromatin, signifying that specific chromatin modifications are involved in establishing that connection. Finally, we have preliminary evidence that the dynamic process that we have uncovered might play a role in the repair of all DNA lesions. We speculate that a microtubule-dependent chromatin mobility provides a proofreading mechanism preventing HDR between non-sister chromatids, possibly by physically pulling apart inappropriate connections. Overall, this thesis presents a novel view on how the dynamic behavior of DNA ends might be required for efficient and accurate repair of DNA lesions.

  PublisherOA PDFDOI

• Long noncoding RNA-dependent control of Myc transcriptional bursting

  Cell Reports · 2025-10-01 · 1 citations

  articleOpen accessSenior author

  Genes are transcribed in short periods of activity, called bursts. Bursts are initiated by enhancer-promoter contacts and dynamically controlled by the levels of enhancer- and promoter-produced RNAs through a negative feedback mechanism. Here, by direct visualization of nascent transcripts, we show that chromatin-associated long noncoding RNAs (lncRNAs) contribute to the regulation of transcriptional bursting. We find that production of Pvt1 raises the baseline of RNA concentration in the locus of the Myc proto-oncogene and acts locally and in a dose-dependent manner to decrease the duration of Myc bursting. Premature termination of Pvt1 led to higher Myc expression and transcriptional activities, resulting in increased cellular proliferation and advanced tumor development in autochthonous models of lung cancer. These findings point to a critical lncRNA-mediated mechanism for Myc regulation and suggest a potentially widespread role for lncRNAs in fine-tuning gene expression through local control of transcriptional bursting.

  PublisherDOI

• Activation of Pvt1b isoform contributes to local Pvt1 abundance to repress Myc during stress

  PLoS Genetics · 2025-07-31 · 1 citations

  articleOpen accessSenior authorCorresponding

  Many long noncoding RNA (lncRNA) loci harbor multiple alternative isoforms. It is not known whether isoform-specific sequence elements enable distinct functions. Previous work identified two alternative transcription start site (TSS) isoforms in the Pvt1 lncRNA locus - the constitutively expressed Pvt1a and the stress-induced Pvt1b. While the function of Pvt1a is not known, the p53-regulated Pvt1b was shown to act locally to repress the transcription of the neighboring Myc proto-oncogene in response to genotoxic and oncogenic stress. Here, we investigated whether Pvt1b contains isoform-specific repressive sequence elements. Our results revealed that Pvt1b contributes to but is not required for Myc repression. Using in vivo and in vitro models of genotoxic and oncogenic stress, we observed that Pvt1a compensates for Pvt1b loss, resulting in Pvt1b deficiency having a moderate effect on Myc regulation, stress response, and tumor suppression. Long-read sequencing exposed a diversity of stress-induced Pvt1a and Pvt1b isoforms, further arguing against a specialized role for Pvt1b. We propose that p53-induced increase in total Pvt1 abundance, and not isoform-specific activation, represses Myc during stress.

  PublisherDOI

• Overexpression of <i>Malat1</i> drives metastasis through inflammatory reprogramming of the tumor microenvironment

  Science Immunology · 2024-06-14 · 29 citations

  articleOpen accessSenior authorCorresponding

  Expression of the long noncoding RNA (lncRNA) metastasis–associated lung adenocarcinoma transcript 1 ( MALAT1 ) correlates with tumor progression and metastasis in many tumor types. However, the impact and mechanism of action by which MALAT1 promotes metastatic disease remain elusive. Here, we used CRISPR activation (CRISPRa) to overexpress MALAT1/Malat1 in patient-derived lung adenocarcinoma (LUAD) cell lines and in the autochthonous K-ras/p53 LUAD mouse model. Malat1 overexpression was sufficient to promote the progression of LUAD to metastatic disease in mice. Overexpression of MALAT1/Malat1 enhanced cell mobility and promoted the recruitment of protumorigenic macrophages to the tumor microenvironment through paracrine secretion of CCL2/Ccl2. Ccl2 up-regulation was the result of increased global chromatin accessibility upon Malat1 overexpression. Macrophage depletion and Ccl2 blockade counteracted the effects of Malat1 overexpression. These data demonstrate that a single lncRNA can drive LUAD metastasis through reprogramming of the tumor microenvironment.

  PublisherOA PDFDOI

• Abstract I001: Long noncoding RNAs at the intersection of cancer pathways

  Molecular Cancer Therapeutics · 2024-11-14

  article1st authorCorresponding

  Abstract There are thousands of long noncoding RNAs (lncRNAs) in mammalian genomes. Yet, their functional significance in health and disease states remains poorly understood. We investigate the intersection of lncRNAs and cancer biology. On the one hand, we dissect the molecular and cellular mechanisms by which lncRNAs modulate cancer pathways. On the other hand, we develop mouse models to interrogate the roles of lncRNAs in tumorigenesis at the organismal level. Our work has uncovered insights into the transcriptional regulatory roles of lncRNAs during the cellular response to genotoxic and oncogenic stress. In parallel, we have elucidated roles of lncRNAs as drivers of tumor progression and metastatic dissemination. The combined functional and mechanistic studies have revealed the importance of lncRNAs in cancer and suggest therapeutic approaches to target lncRNAs or their downstream effectors in cancer. Citation Format: Nadya Dimitrova. Long noncoding RNAs at the intersection of cancer pathways [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr I001.

  PublisherDOI

• Therapeutic Inhibition of <i>LincRNA-p21</i> Protects Against Cardiac Hypertrophy

  Circulation Research · 2024-06-12 · 14 citations

  articleOpen access

  BACKGROUND: Cardiac hypertrophy is an adaptive response to pressure overload aimed at maintaining cardiac function. However, prolonged hypertrophy significantly increases the risk of maladaptive cardiac remodeling and heart failure. Recent studies have implicated long noncoding RNAs in cardiac hypertrophy and cardiomyopathy, but their significance and mechanism(s) of action are not well understood. METHODS: We measured lincRNA-p21 RNA and H3K27ac levels in the hearts of dilated cardiomyopathy patients. We assessed the functional role of lincRNA-p21 in basal and surgical pressure-overload conditions using loss-of-function mice. Genome-wide transcriptome analysis revealed dysregulated genes and pathways. We labeled proteins in proximity to full-length lincRNA-p21 using a novel BioID2-based system. We immunoprecipitated lincRNA-p21-interacting proteins and performed cell fractionation, ChIP-seq (chromatin immunoprecipitation followed by sequencing), and co-immunoprecipitation to investigate molecular interactions and underlying mechanisms. We used GapmeR antisense oligonucleotides to evaluate the therapeutic potential of lincRNA-p21 inhibition in cardiac hypertrophy and associated heart failure. RESULTS: lincRNA-p21 was induced in mice and humans with cardiomyopathy. Global and cardiac-specific lincRNA-p21 knockout significantly suppressed pressure overload-induced ventricular wall thickening, stress marker elevation, and deterioration of cardiac function. Genome-wide transcriptome analysis and transcriptional network analysis revealed that lincRNA-p21 acts in trans to stimulate the NFAT/MEF2 (nuclear factor of activated T cells/myocyte enhancer factor-2) pathway. Mechanistically, lincRNA-p21 is bound to the scaffold protein KAP1 (KRAB-associated protein-1). lincRNA-p21 cardiac-specific knockout suppressed stress-induced nuclear accumulation of KAP1, and KAP1 knockdown attenuated cardiac hypertrophy and NFAT activation. KAP1 positively regulates pathological hypertrophy by physically interacting with NFATC4 to promote the overactive status of NFAT/MEF2 signaling. GapmeR antisense oligonucleotide depletion of lincRNA-p21 similarly inhibited cardiac hypertrophy and adverse remodeling, highlighting the therapeutic potential of inhibiting lincRNA-p21 . CONCLUSIONS: These findings advance our understanding of the functional significance of stress-induced long noncoding RNA in cardiac hypertrophy and demonstrate the potential of lincRNA-p21 as a novel therapeutic target for cardiac hypertrophy and subsequent heart failure.

  PublisherOA PDFDOI

• Challenges in LncRNA Biology: Views and Opinions

  Non-Coding RNA · 2024-08-01 · 12 citations

  articleOpen access

  This is a mini-review capturing the views and opinions of selected participants at the 2021 IEEE BIBM 3rd Annual LncRNA Workshop, held in Dubai, UAE. The views and opinions are expressed on five broad themes related to problems in lncRNA, namely, challenges in the computational analysis of lncRNAs, lncRNAs and cancer, lncRNAs in sports, lncRNAs and COVID-19, and lncRNAs in human brain activity.

  PublisherOA PDFDOI

• Transcription regulation by long non-coding RNAs: mechanisms and disease relevance

  Nature Reviews Molecular Cell Biology · 2024 · 290 citations

  Senior authorCorresponding
  • Biology
  • Genetics
  • Computational biology
  PublisherOA PDFDOI

• Data from Stromal Expression of miR-143/145 Promotes Neoangiogenesis in Lung Cancer Development

  2023-04-03

  preprintOpen access1st authorCorresponding

  &lt;div&gt;Abstract&lt;p&gt;The two unrelated miRNAs miR-143 and miR-145, coexpressed from the &lt;i&gt;miR-143/145&lt;/i&gt; cluster, have been proposed to act as tumor suppressors in human cancer, and therapeutic benefits of delivering miR-143 and miR-145 to tumors have been reported. In contrast, we found that tumor-specific deletion of miR-143/145 in an autochthonous mouse model of lung adenocarcinoma did not affect tumor development. This was consistent with the lack of endogenous &lt;i&gt;miR-143/145&lt;/i&gt; expression in normal and transformed lung epithelium. Surprisingly, miR-143/145 in the tumor microenvironment dramatically promoted tumor growth by stimulating the proliferation of endothelial cells. Loss of miR-143/145 &lt;i&gt;in vivo&lt;/i&gt; led to derepression of the miR-145 target CAMK1D, an inhibitory kinase, which when overexpressed prevents mitotic entry of endothelial cells. As a consequence, tumors in miR-143/145-deficient animals exhibited diminished neoangiogenesis, increased apoptosis, and their expansion was limited by the tumor's ability to co-opt the alveolar vasculature. These findings demonstrate that stromal miR-143/145 promotes tumorigenesis and caution against the use of these miRNAs as agents in cancer therapeutics.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Significance:&lt;/b&gt; This study shows that miR-143/145 expressed from the tumor microenvironment stimulates neoangiogenesis and supports tumor expansion in the lung, demonstrating a surprising role for the putative tumor suppressor miRNA cluster in promoting tumorigenesis. We propose inhibition of miR-143/145 as a therapeutic avenue to modulate tumor neoangiogenesis. &lt;i&gt;Cancer Discov; 6(2); 188–201. ©2015 AACR&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;This article is highlighted in the In This Issue feature, p. 109&lt;/p&gt;&lt;/div&gt;

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Recent grants

• Roles and mechanisms of cis-regulatory IncRNAs in the p53 tumor suppressor pathway

  NIH · $2.5M · 2018–2025

Frequent coauthors

• Tyler Jacks

  Massachusetts Institute of Technology

  19 shared

• Fernando J. de Miguel

  17 shared

• Katerina Politi

  17 shared

• Jesse R. Zamudio

  Institute of Molecular Biology

  12 shared

• Elena Martínez‐Terroba

  12 shared

• D. Gary Gilliland

  University of California, Los Angeles

  11 shared

• Camila Robles-Oteíza

  9 shared

• Benjamin L. Ebert

  9 shared

Education

• postdoctoral, Koch Institute for Integrative Cancer Research

  Massachusetts Institute of Technology

  2015

• Ph.D.

  Rockefeller University

  2009

• Sc.B.

  Brown University

  2002

Awards & honors

• Harold M. Weintraub Graduate Student Award
• HHMI Predoctoral Fellowship
• Damon Runyon Postdoctoral Fellowship Award
• Lung Cancer Research Foundation 2016 Scientific Merit Award