Abdol H. Rezaeian

Harvard Medical School | HMS · Department of Pathology

Circadian clock orchestrates the intergenic biochemical, physiological and behavioral changes to form an approximate 24h oscillation through the transcription-translation feedback loop (TTFL). Mechanistically, a heterodimer of transcriptional activator formed by BMAL1 and CLOCK, governs the expression of its transcriptional repressors, CRY, PER and...

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype accounting for around 15% of all breast cancer patients and is responsible for 30% of breast cancer-related deaths. Although chemotherapy is the mainstay therapy for TNBC, development of resistance significantly reduces patients’ survival. Therefore, there is an urgen...

SKP2, an F-box protein of the SCF type of the E3 ubiquitin ligase complex, plays an important function in driving tumorigenesis through the destruction of numerous tumor-suppressive proteins. Besides its critical role in cell cycle regulation, proto-oncogenic functions of SKP2 have also been shown in a cell cycle regulation-independent manner. Ther...

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype. It accounts for ~15% of all breast cancer patients yet is responsible for 30% of breast cancer deaths. TNBC is treated primarily with conventional chemotherapy; however, resistance to therapy is common, leading to high mortality rates. Importantly, the benefit of cur...

Despite the knowledge that protein translation and various metabolic reactions that create and sustain cellular life occur in the cytoplasm, the structural organization within the cytoplasm remains unclear. Recent models indicate that cytoplasm contains viscous fluid and elastic solid phases. We separated these viscous fluid and solid elastic compa...

The recent findings advance our knowledge for the prevention of the premature activation of the major oncogenic pathways including MYC and the cyclin D-cyclin-dependent kinases 4 and 6 (CDK4/6) axis. D-type cyclins are frequently deregulated in human cancer and promote cell division in part through activation of CDK4/6. Therefore, the activation of...

Maintaining neuronal integrity and function requires precise mechanisms controlling organelle and protein quality. Alzheimer’s disease (AD) is also characterized by functional defects in the clearance and recycling of intracellular components. In fact, neuronal homeostasis involves autophagy, mitophagy, apoptosis, and compromised activity in these...

Neurodegenerative diseases are characterized by the progression of neuronal degeneration, resulting in dysfunction of cognition and mobility. Many neurodegenerative diseases are due to proteinopathies arising from unusual protein accumulation and aggregation. The aggregation of misfolded proteins, such as β-amyloid, α-synuclein, tau, and polyglutam...

ATM is among of the most critical initiators and coordinators of the DNA-damage response. ATM canonical and non-canonical signaling pathways involve hundreds of downstream targets that control many important cellular processes such as DNA damage repair, apoptosis, cell cycle arrest, metabolism, proliferation, oxidative sensing, among others. Of not...

Chemoresistance is a major obstacle in the treatment of triple negative breast cancer (TNBC), the most aggressive breast cancer subtype. To overcome chemoresistance, we have selected TNBC tumors for chemotherapy resistance in vivo, characterized their transcriptomes by RNA-sequencing and identified hypoxia-induced ECM re-modeler, lysyl oxidase (LOX...

Cancer metastasis accounts for the major cause of cancer-related deaths. How disseminated cancer cells cope with hostile microenvironments in secondary site for full-blown metastasis is largely unknown. Here, we show that AMPK (AMP-activated protein kinase), activated in mouse metastasis models, drives pyruvate dehydrogenase complex (PDHc) activati...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The ataxia-telangiectasia mutated (ATM) protein kinase is widely known for its function as a chief mobilizer of the DNA damage response (DDR) upon DNA double-strand breaks. ATM orchestrates the DDR by modulating the expression of various microRNAs (miRNAs) through several mechanisms. On the other hand, a set of miRNAs contribute to tight regulation...

The ataxia-telangiectasia mutated (ATM) protein kinase is widely known for its function as a chief mobilizer of the DNA damage response (DDR) upon DNA double-strand breaks. ATM orchestrates the DDR by modulating the expression of various microRNAs (miRNAs) through several mechanisms. On the other hand, a set of miRNAs contribute to tight regulation...

HIF1α is a critical factor for transcriptional activation of several oncogenes in many cancers. Since 1994 and after discovery of HIF1α, scientists didn’t know how HIF1α protein is stabilized in the nucleus after translocation upon hypoxia. Moreover, it was believed that histone H2AX which is known as a master regulator of DNA damage repair, is a t...

HIF1α is a critical factor for transcriptional activation of several oncogenes in many cancers. Since 1994 and after discovery of HIF1α, scientists didn’t know how HIF1α protein is stabilized in the nucleus after translocation upon hypoxia. Moreover, it was believed that histone H2AX which is known as a master regulator of DNA damage repair, is a t...

HIF1α is a critical factor for transcriptional activation of several oncogenes in many cancers. Since 1994 and after discovery of HIF1α, scientists didn’t know how HIF1α protein is stabilized in the nucleus after translocation upon hypoxia. Moreover, it was believed that histone H2AX which is known as a master regulator of DNA damage repair, is a t...

HIF1α is a critical factor for transcriptional activation of several oncogenes in many cancers. Since 1994 and after discovery of HIF1α, scientists didn’t know how HIF1α protein is stabilized in the nucleus after translocation upon hypoxia. Moreover, it was believed that histone H2AX which is known as a master regulator of DNA damage repair, is a t...

HIF1α is a critical factor for transcriptional activation of several oncogenes in many cancers. Since 1994 and after discovery of HIF1α, scientists didn’t know how HIF1α protein is stabilized in the nucleus after translocation upon hypoxia. Moreover, it was believed that histone H2AX which is known as a master regulator of DNA damage repair, is a t...

HIF1α is a critical factor for transcriptional activation of several oncogenes in many cancers. Since 1994 and after discovery of HIF1α, scientists didn’t know how HIF1α protein is stabilized in the nucleus after translocation upon hypoxia. Moreover, it was believed that histone H2AX which is known as a master regulator of DNA damage repair, is a t...

HIF1α is a critical factor for transcriptional activation of several oncogenes in many cancers. Since 1994 and after discovery of HIF1α, scientists didn’t know how HIF1α protein is stabilized in the nucleus after translocation upon hypoxia. Moreover, it was believed that histone H2AX which is known as a master regulator of DNA damage repair, is a t...

HIF1α is a critical factor for transcriptional activation of several oncogenes in many cancers. Since 1994 and after discovery of HIF1α, scientists didn’t know how HIF1α protein is stabilized in the nucleus after translocation upon hypoxia. Moreover, it was believed that histone H2AX which is known as a master regulator of DNA damage repair, is a t...

Although deletion of certain autophagy-related genes has been associated with defects in hematopoiesis, it remains unclear whether hyperactivated mitophagy affects the maintenance and differentiation of hematopoietic stem cells (HSCs) and committed progenitor cells. Here we report that targeted deletion of the gene encoding the AAA+-ATPase Atad3a h...

Dynamic changes in histone modifications under various physiological cues play important roles in gene transcription and cancer. Identification of new histone marks critical for cancer development is of particular importance. Here we show that, in a glucose-dependent manner, E3 ubiquitin ligase NEDD4 ubiquitinates histone H3 on lysine 23/36/37 resi...

Supplementary Figures

HIF-1/hypoxia signaling regulates diverse biological processes, such as glycolysis, angiogenesis, and invasion leading to promoting cancer progression, metastasis and therapy resistance. Understanding the mechanisms by which HIF- 1/hypoxia signaling is regulated may provide the new paradigms and strategies for cancer therapy and overcoming drug r...

HIF1α is a critical factor for transcriptional activation of several oncogenes in many cancers. Since 1994 and after discovery of HIF1α, scientists didn’t know how HIF1α protein is stabilized in the nucleus after translocation upon hypoxia. Moreover, it was believed that histone H2AX which is known as a master regulator of DNA damage repair, is a t...

The understanding of how hypoxia stabilizes and activates HIF1α in the nucleus with related oncogenic signals could revolutionize targeted therapy for cancers. Here, we find that histone H2AX displays oncogenic activity by serving as a crucial regulator of HIF1α signalling. H2AX interacts with HIF1α to prevent its degradation and nuclear export in...

Mitochondrial p53 is involved in apoptosis and tumor suppression. However, its regulation is not well studied. Here, we show that TRAF6 E3 ligase is a crucial factor to restrict mitochondrial translocation of p53 and spontaneous apoptosis by promoting K63-linked ubiquitination of p53 at K24 in cytosol, and such ubiquitination limits the interaction...

The regulation of RagA(GTP) is important for amino-acid-induced mTORC1 activation. Although GATOR1 complex has been identified as a negative regulator for mTORC1 by hydrolyzing RagA(GTP), how GATOR1 is recruited to RagA to attenuate mTORC1 signaling remains unclear. Moreover, how mTORC1 signaling is terminated upon amino acid stimulation is also un...

Understanding the mechanism by which cell growth, migration, polyploidy, and tumorigenesis are regulated may provide important therapeutic strategies for cancer therapy. Here we identify the Skp2-macroH2A1 (mH2A1)-cyclin-dependent kinase 8 (CDK8) axis as a critical pathway for these processes, and deregulation of this pathway is associated with hum...

LKB1 is activated by forming a heterotrimeric complex with STRAD and MO25. Recent studies suggest that LKB1 has pro-oncogenic functions, besides acting as a tumor suppressor. How the LKB1 activity is maintained and how LKB1 regulates cancer development are largely unclear. Here we show that K63-linked LKB1 polyubiquitination by Skp2-SCF ubiquitin l...

The Grb2-associated binding protein 1 (GAB1) integrates signals from different signaling pathways and is over-expressed in many cancers, therefore representing a new therapeutic target. In the present study, we aim to target the pleckstrin homology (PH) domain of GAB1 for cancer treatment. Using homology models we derived, high-throughput virtual s...

Akt regulates critical cellular processes including cell survival and proliferation, glucose metabolism, cell migration, cancer progression and metastasis through phosphorylation of a variety of downstream targets. The Akt pathway is one of the most prevalently hyperactivated signaling pathways in human cancer, thus, research deciphering molecular...

Background Resistance to Fas-mediated apoptosis limits the efficacy of currently available chemotherapy regimens. We identified CD74, which is known to be overexpressed in hematological malignancies, as one of the factors interfering with Fas-mediated apoptosis. Methods CD74 expression was suppressed in human B-lymphoma cell lines, BJAB and Raji,...

MicroRNAs have emerged as important post-transcriptional regulators of gene expression. Identification of cancer-regulated microRNAs or other classes of endogenous small RNAs have advanced our knowledge in cancer progression and metastasis. Among many tools, small RNA cloning is a powerful method to identify new microRNAs (miRNAs) and to profile mi...

MicroRNAs have emerged as important post-transcriptional regulators of gene expression. Identification of cancer-regulated microRNAs or other classes of endogenous small RNAs have advanced our knowledge in cancer progression and metastasis. Among many tools, small RNA cloning is a powerful method to identify new microRNAs (miRNAs) and to profile mi...

There is a pressing need to identify prognostic markers of metastatic disease and targets for treatment. Combining high-throughput RNA sequencing, functional characterization, mechanistic studies and clinical validation, we identify leukemia inhibitory factor receptor (LIFR) as a breast cancer metastasis suppressor downstream of the microRNA miR-9...

Objective: To determine the geographical distribution of Leishmania species causing cutaneous leishmaniasis (CL) and to study the genetic heterogeneity of Leishmania major isolates from different endemic areas of Iran. Methods: A total of 341 isolates from lesions of patients living in 11 provinces of Iran were grown in culture medium and inocul...

The Mre11/Rad50/NBS1 (MRN) complex is thought to be a critical sensor that detects damaged DNA and recruits ATM to DNA foci for activation. However, it remains to be established how the MRN complex regulates ATM recruitment to the DNA foci during DNA double-strand breaks (DSBs). Here we show that Skp2 E3 ligase is a key component for the MRN comple...

Skp2 (S-phase kinase-associated protein-2) SCF complex displays E3 ligase activity and oncogenic activity by regulating protein ubiquitination and degradation, in turn regulating cell cycle entry, senescence and tumorigenesis. The maintenance of the integrity of Skp2 SCF complex is critical for its E3 ligase activity. The Skp2 F-box protein is a ra...

Defective Fas signaling leads to resistance to various anticancer therapies. Presence of potential inhibitors of Fas which could block Fas signaling can explain cancer cells resistance to apoptosis. We identified promyelocytic leukemia protein (PML) as a Fas-interacting protein using mass spectrometry analysis. The function of PML is blocked by its...

The calcitonin gene-related peptides (CGRP), alphaCGRP and betaCGRP, have been implicated to play various roles in primates and rodent. However, since the expression information has been limited, in the present study, we measured the amount of gene expression in mouse brain, liver, kidney, heart, and testis at embryonic day (E) 14, E17, postnatal d...

Calcitonin (CT) has been shown to have various functions including osteoclast activity and calcium and phosphorus metabolism in mammals. In the present study, we measured the amounts of CT mRNA in the mouse brain, liver, kidney, heart and testis at various development stages, 14 days post-coitum (dpc), 17-dpc, newborn, 1 week and 8 weeks (adult), u...

HIF1α is a critical factor for transcriptional activation of several oncogenes in many cancers. Since 1994 and after discovery of HIF1α, scientists didn’t know how HIF1α protein is stabilized in the nucleus after translocation upon hypoxia. Moreover, it was believed that histone H2AX which is known as a master regulator of DNA damage repair, is a t...

A large number of significant QTL for economically important traits including average daily gain have been located on SSC1q, which, as shown by chromosome painting, corresponds to four human chromosomes (HSA9, 14, 15 and 18). To provide a comprehensive comparative map for efficient selection of candidate genes, 81 and 34 genes localized on HSA9 and...

Recently we identified and characterized porcine calcitonin receptor-stimulating peptide (CRSP) 1, CRSP2 and CRSP3 as members of the calcitonin/calcitonin gene-related peptide (CT/CGRP) family. In the present study, the genomic sequences and organization of CRSP1, 2, and 3 were determined, and the expression of the genes in the porcine brain was in...

Recently, it has been reported that antisense RNAs are transcribed from a large number of genes in various species including human and mouse. The Prdx2 gene, which is indicated to be involved in signal transduction related to platelet-derived growth factor as well as to protection from oxidizing agents, has been shown to produce sense and antisense...

Using dinucleotide repeats for carrier detection and prenatal diagnosis of haemophilia A patients, led us to find different alleles and their frequencies in Iranian population. Polymerase chain reaction (PCR) amplification of two short tandem repeat (STR) loci of factor VIII (FVIII) gene was performed, and the PCR products were resolved on 10% nati...

AbstractBackground: Determination of transgenic embryos from non transgenic embryos sibling is an important step in producing homozygous transgenic mice. These steps need by PCR or southern blotting followed extraction of DNA, but both techniques require skill and consume time.Objective: The aim of this study was simulation of high accuracy method...

The mouse TNF locus comprises tandemly arranged genes coding for Tnf alpha (cachectin) and Tnf ß (lymphotoxin). The mouse TNF and Cypla2 loci were selected to detect simple sequence length polymorphism on genomic DNAs of four laboratory mouse strains. These polymorphisms might be useful in the search for tumor supressor genes involved in specific c...