Pk Puvvula

• PhD
• Principal Scientist at Kodikaz Therapeutic Solutions

The exchange of genes between cells is known to play an important physiological and pathological role in many organisms. We show that circulating tumor DNA (ctDNA) facilitates cell-specific gene transfer between human cancer cells and explain part of the mechanisms behind this phenomenon. As ctDNA migrates into the nucleus, genetic information is t...

Pancreatic ductal adenocarcinoma (PC) is the fourth most common cancer-related cause of death in Western countries. It is projected that PC will become the second most prevalent cause of cancer-related mortality by the year 2030. Although chemotherapy may offer certain advantages to those who have been diagnosed with pancreatic cancer, its effectiv...

Introduction We have demonstrated that transposons derived from ctDNA can be transferred between cancer cells. The present research aimed to investigate the cellular uptake and intracellular trafficking of Multiple Myeloma-zip code (MM-ZC), a cell-specific zip code, in myeloma cell lines. We demonstrated that MM-ZC uptake by myeloma cells was conce...

We performed a forward genetic screen to discover peptides that specifically target breast cancer cells using a Penetratin tagged, random 15mer peptide library. We identified a group of novel peptides that specifically inhibited the proliferation and survival of breast cancer cells without affecting normal primary mammary epithelial cells or fibrob...

Multiple myeloma is a heterogeneous malignant plasma cell disorder with complex molecular and genetic abnormalities. Significant advances have been made in the treatment of multiple myeloma; however, a large proportion of patients fail to attain a favorable response and relapse. Due to efficacy and toxicity, the development of drug conjugates for m...

A variety of organisms have been shown to have altered physiology or developed pathology as a result of gene transfer, but mammals has never been shown to do so. Here, we show that circulating tumor DNA (ct) can promote cell-specific horizontal gene transfer (HGT) between human cancer cells and explain the mechanisms behind this phenomenon. Once ct...

hnRNPK is a multifunctional protein that plays an important role in cancer cell proliferation and metastasis via its RNA- and DNA-binding properties. Previously we showed that cell-penetrating peptides derived from the RGG RNA-binding domain of SAFA (hnRNPU) disrupt cancer cell proliferation and survival. Here we explore the efficacy of a peptide d...

RBM39 is a known splicing factor and coactivator. Here, we report that RBM39 functions as a master transcriptional regulator that interacts with the MLL1 complex to facilitate chromatin binding and H3K4 trimethylation in breast cancer cells. We identify RBM39 functional domains required for DNA and complex binding and show that the loss of RBM39 ha...

Scaffold-attachment-factor A (SAFA) has important roles in many normal and pathologic cellular processes but the scope of its function in cancer cells is unknown. Here, we report dominant-negative activity of novel peptides derived from the SAP and RGG-domains of SAFA and their effects on proliferation, survival and the epigenetic landscape in a ra...

In this article, we provide a brief summary of work by us and others to discover the molecular underpinnings of early conduction system development and function. We focus on how the multifunctional protein Tbx3 contributes to acquisition and homeostasis of the tissue-specific properties of the sinoatrial and atrioventricular nodes. We also provide...

Long noncoding RNAs (lncRNAs) are a class of transcripts longer than 200 nucleotides with no open reading frame. They play a key role in the regulation of cellular processes such as genome integrity, chromatin organization, gene expression, translation regulation, and signal transduction. Recent studies indicated that lncRNAs are not only dysregula...

Pluripotency represents a cell state comprising a fine-tuned pattern of transcription factor activity required for embryonic stem cell (ESC) self-renewal. TBX3 is the earliest expressed member of the T-box transcription factor family and is involved in maintenance and induction of pluripotency. Hence, TBX3 is believed to be a key member of the plur...

Table S2. Differentially Regulated Genes between TBX3GFP-High and -Low Cells Referred to 2i-Treated ESCs

Table S7. Upregulated Genes between TBX3GFP-High and -Low ESCs Cultivated Under 2i/LIF Conditions

Table S5. Upregulated Genes between TBX3-Null ESCs and Wild-Type ESCs Cultivated Under 2i/LIF Conditions

Table S8. Downregulated Genes between TBX3GFP-High and -Low ESCs Cultivated Under 2i/LIF Conditions

Table S6. Downregulated Genes between TBX3-Null ESCs and Wild-Type ESCs Cultivated Under 2i/LIF Conditions

Piwi-interacting RNAs (piRNAs), a class of 26- to 32-nt non-coding RNAs (ncRNAs), function in germline development, transposon silencing, and epigenetic regulation. We performed deep sequencing and annotation of untreated and periodate-treated small RNA cDNA libraries from human fetal and adult germline and reference somatic tissues. This revealed...

Cellular senescence is a stable cell cycle arrest that inhibits the outgrowth of pre-cancerous cells but is also implicated in wound healing, embryonic development, aging and age-related pathologies. Our knowledge on gene regulatory circuits that establish and maintain the senescence phenotype is highly fragmentary. Here, we provide several lines o...

Cellular senescence is a stable cell cycle arrest that limits the proliferation of pre-cancerous cells. Here we demonstrate that scaffold-attachment-factor A ( SAFA) and the long noncoding RNA PANDA differentially interact with polycomb repressive complexes (PRC1 and PRC2) and the transcription factor NF-YA to either promote or suppress senescence....

Determining the statistical significance of shared differentially expressed genes using the hypergeometric test, as implemented in the R statistical language (phyper).DOI: http://dx.doi.org/10.7554/eLife.02805.029

Differentially expressed genes after knockdown of CAPERα in HFFs detected by RNA-Seq.DOI: http://dx.doi.org/10.7554/eLife.02805.027

Differentially expressed genes after knockdown of TBX3 in HFFs detected by RNA-Seq.DOI: http://dx.doi.org/10.7554/eLife.02805.028

Author Summary TBX3 is a protein with essential roles in development and tissue homeostasis, and is implicated in cancer pathogenesis. TBX3 mutations in humans cause a complex of birth defects called Ulnar-mammary syndrome (UMS). Despite the importance of TBX3 and decades of investigation, few TBX3 partner proteins have been identified and little i...

The special AT-rich DNA-binding protein 1 (SATB1) is a matrix attachment region (MAR)-binding protein that acts as a global repressor via recruitment of CtBP1:HDAC1-containing co-repressors to its binding targets. The N-terminal PSD95/Dlg-A/ZO-1 (PDZ)-like domain of SATB1 mediates interactions with several chromatin proteins. In the present study,...

The chromatin organizer SATB1 regulates distant genes by selectively tethering matrix attachment regions (MARs) to the nuclear matrix. Post-translational modifications (PTMs) are important regulators of functional activities of proteins. Recently, a phosphorylation-dependent molecular switch that provided insights into the molecular mechanism of tr...

A novel Gram-negative, rod-shaped, non-motile bacterium, designated strain LW7(T), was isolated from a water sample collected at a depth of 4.5 m from Lonar Lake in Buldhana district, Maharastra, India. The cell suspension was dark-reddish orange due to the presence of carotenoids. The fatty acids were dominated by large amounts of iso-C₁₅:₀ (59.6...

Special AT-rich binding protein 1 (SATB1) acts as a global regulator of gene expression by recruiting various corepressor or coactivator complexes, thereby establishing a unique chromatin structure at its genomic targets in a context-dependent manner. Although SATB1 acts predominantly as a repressor via recruitment of histone deacetylase 1 (HDAC1)...

To better understand DNA recognition and transcription activity by SATB1, the T-lineage-enriched chromatin organizer and transcription factor, we have determined its optimal DNA-binding sequence by random oligonucleotide selection. The consensus SATB1-binding sequence (CSBS) comprises a palindromic sequence in which two identical AT-rich half-sites...

Compartmentalized distribution of functional components is a hallmark of the eukaryotic nucleus. Technological advances in recent years have provided unprecedented insights into the role of chromatin organization and interactions of various structural-functional components toward gene regulation. SATB1, the global chromatin organizer and transcript...

The function of the subnuclear structure the promyelocytic leukaemia (PML) body is unclear largely because of the functional heterogeneity of its constituents. Here, we provide the evidence for a direct link between PML, higher-order chromatin organization and gene regulation. We show that PML physically and functionally interacts with the matrix a...

Retroviral integration has recently been shown to be nonrandom, favoring transcriptionally active regions of chromatin. However, the mechanism for integration site selection by retroviruses is not clear. We show here the occurrence of Alu-like motifs in the sequences flanking the reported viral integration sites that are significantly different fro...

SATB1 regulates gene expression by acting as a "docking site" for several chromatin remodeling enzymes and also by recruiting corepressors (HDACs) or coactivators (HATs) directly to promoters. However, how these contrasting effectors act at the level of SATB1 is not clear. We show here that phosphorylation by PKC acts as a switch to determine wheth...

One hallmark of human immunodeficiency virus type 1 (HIV-1) infection is the dysregulation of cytokine gene expression in T cells. Transfection of T cells with human T-cell leukemia type 1 or 2 transactivator results in the induction of the T-cell-restricted cytokine interleukin-2 (IL-2) and its receptor (IL-2Ralpha). However, no T-cell-specific fa...

The chromatin environment and the sites of integration in the host genome are critical determinants of human immunodeficiency virus (HIV) transcription and replication. Depending on the chromosomal location of provirus integration within the genome, HIV-1 long terminal repeat (LTR)-mediated transcription may vary from 0- to 70-fold. Cis-elements su...