Hamid Band

University of Nebraska Medical Center | UNMC · Eppley Institute for Cancer Research

While better management of loco-regional prostate cancer (PC) has greatly improved survival, advanced PC remains a major cause of cancer deaths. Identification of novel targetable pathways that contribute to tumor progression in PC could open new therapeutic options. The di-ganglioside GD2 is a target of FDA-approved antibody therapies in neuroblas...

RUVB-like protein 1 (RUVBL1) belongs to an ATPase family known as AAA proteins (ATPases associated with diverse cellular activities). It can act independently or through participation in variable multi-subunit complexes as HSP90 co-chaperone complex R2TP, together with RUVBL2, RPAP3 and PIH1D1, and "PAQosome" for particle for arrangement of quatern...

In this study, we identify USP1 as a transcriptional target of EWS::FLI1 and demonstrate the requisite function of USP1 in Ewing sarcoma (EWS) cell survival in response to endogenous replication stress. EWS::FLI1 oncogenic transcription factor drives most EWS, a pediatric bone cancer. EWS cells display elevated levels of R-loops and replication str...

Overexpression of the EPS15 Homology Domain containing 1 (EHD1) protein has been linked to tumorigenesis but whether its core function as a regulator of intracellular traffic of cell surface receptors plays a role in oncogenesis remains unknown. We establish that EHD1 is overexpressed in Ewing sarcoma (EWS), with high EHD1 mRNA expression specifyin...

Bioinks for 3D bioprinting of tumor models should not only meet printability requirements but also accurately maintain and support phenotypes of tumor surrounding cells to recapitulate key tumor hallmarks. Collagen is a major extracellular matrix protein for solid tumors, but low viscosity of collagen solution has made 3D bioprinted cancer models c...

Among the signaling pathways that control the stem cell self-renewal and maintenance vs. acquisition of differentiated cell fates, those mediated by receptor tyrosine kinase (RTK) activation are well established as key players. CBL family ubiquitin ligases are negative regulators of RTKs but their physiological roles in regulating stem cell behavio...

While better management of loco-regional prostate cancer (PC) has greatly improved survival, advanced PC remains a major cause of cancer deaths. Novel, targetable, pathways that contribute to tumorigenesis in advanced PC could open new therapeutic options. The di-ganglioside GD2 is a target of FDA-approved antibody therapies in neuroblastoma, but a...

We previously established a requirement of the EPS15 Homology Domain containing 1 (EHD1) protein in optimal cell surface expression and physiological signaling of receptor tyrosine kinase (RTKs), but any contribution of this mechanism to oncogenesis is unknown. Here, we show that EHD1 is overexpressed in Ewing sarcoma (EWS), with high EHD mRNA expr...

With nearly all cancer deaths a result of metastasis, elucidating novel pro-metastatic cellular adaptations could provide new therapeutic targets. Here, we show that overexpression of the EPS15-Homology Domain-containing 2 (EHD2) protein in a large subset of breast cancers (BCs), especially the triple-negative (TNBC) and HER2+ subtypes, correlates...

With nearly all cancer deaths a result of metastasis, elucidating novel pro-metastatic cellular adaptations could provide new therapeutic targets. Here, we show that overexpression of the EPS15-Homology Domain-containing 2 (EHD2) protein in a large subset of BCs, especially the triple-negative (TNBC) and HER2+ subtypes, correlates with shorter pati...

Background & Significance: Prostate cancer (PCa) is the second leading cause of cancer deaths (~34,000 in 2021 (ACS)) in American men. Castration resistance and resistance to the next-gen androgen receptor (AR) targeted drugs are major challenges. Castration resistance involves multiple mechanisms, including androgen-independent signaling by androg...

Background: Ewing Sarcoma (EWS) is the second most common malignant bone tumor of children and adolescents. Patients with metastatic or recurrent disease have very poor outcomes. The receptor tyrosine kinase (RTK) insulin-like growth factor 1 receptor (IGF1R) has been implicated in EWS tumorigenesis and development of metastatic disease, with anti-...

Ecdysoneless (ECD) protein is essential for embryogenesis, cell-cycle progression, and cellular stress mitigation with an emerging role in mRNA biogenesis. We have previously shown that ECD protein as well as its mRNA are overexpressed in breast cancer and ECD overexpression predicts shorter survival in patients with breast cancer. However, the gen...

High-risk human papillomaviruses (HPV), exemplified by HPV16/18, are causally linked to human cancers of the anogenital tract, skin, and upper aerodigestive tract. Previously, we identified Ecdysoneless (ECD) protein, the human homolog of the Drosophila ecdysoneless gene, as a novel HPV16 E6–interacting protein. Here, we show that ECD, through its...

Overexpression of the epidermal growth factor receptor (EGFR) family member ErbB2 (HER2) drives oncogenesis in up to 25% of invasive breast cancers. ErbB2 expression at the cell surface is required for oncogenesis but mechanisms that ensure the optimal cell surface display of overexpressed ErbB2 following its biosynthesis in the endoplasmic reticul...

The mammalian orthologue of Ecdysoneless (ECD) protein is required for embryogenesis, cell cycle progression, and mitigation of ER stress. Here, we identified key components of the mRNA export complexes as binding partners of ECD and characterized the functional interaction of ECD with key mRNA export-related DEAD BOX protein helicase DDX39A. We fi...

EGFR is a prototype receptor tyrosine kinase and an oncogene in many solid tumors. Cell surface display of EGFR is essential for cellular responses to its ligands. While post-activation endocytic traffic of EGFR has been well elucidated, little is known about mechanisms of basal/pre-activation surface display of EGFR. Here, we identify a novel role...

RUVB-like protein 2 (RUVBL2)/Reptin is a member of ATPase family, and participates in multi-subunit complexes as R2TP complex, together with RUVBL1, RPAP3 and PIH1D1, and "PAQosome" for particle for arrangement of quaternary structure.  It interacts with key carcinogenic machineries and is involved in an array of diverse cellular functions. It aff...

Purpose Negative surgical margins (NSMs) have favorable prognostic implications in breast tumor resection surgery. Fluorescence image-guided surgery (FIGS) has the ability to delineate surgical margins in real time, potentially improving the completeness of tumor resection. We have recently developed indocyanine green (ICG)-loaded self-assembled hy...

The AP-2γ transcription factor, encoded by the TFAP2C gene, regulates the expression of estrogen receptor-alpha (ERα) and other genes associated with hormone response in luminal breast cancer. Little is known about the role of AP-2γ in other breast cancer subtypes. A subset of HER2+ breast cancers with amplification of the TFAP2C gene locus becomes...

Purpose of the study: Workers in enclosed hogbarns experience an increased incidence of airway inflammation and obstructive lung disease, and an aqueous hogbarn dust extract (HDE) induces multiple inflammation-related responses in cultured airway epithelial cells. Epidermal growth factor receptor (EGFR) phosphorylation and activation has been iden...

Adipose derived mesenchymal stem/stromal cells (ADMSC) are one of the major stromal cells in the breast cancer microenvironment to promote cancer progression. Previous studies using two-dimensional (2D) cultures on the effects of ADMSC on breast cancer metastasis and drug resistance remained inconclusive. In the present study, we compared co-cultur...

Eps15 homology domain‐containing protein 4 (EHD4) is an important regulator of endocytic recycling and is abundantly expressed within the inner medullary collecting duct (IMCD). We have previously found that global EHD4 knockout (EHD4‐KO) mice have a higher urine flow and lower urine osmolality as compared to wild‐type (WT) C57Bl/6 mice, but no sig...

Although macrophages are armed with potent antibacterial functions, Mycobacterium tuberculosis (Mtb) replicates inside these innate immune cells. Determinants of macrophage intrinsic bacterial control, and the Mtb strategies to overcome them, are poorly understood. To further study these processes, we used an affinity tag purification mass spectrom...

Solid tumors are 3D assemblies of cancer cells, together with multiple stromal cell types within an extracellular matrix. Yet, the vast majority of cell-based studies to characterize oncogenesis and discovery of new anti-cancer drugs is conducted using conventional 2D monolayer culture systems, where cells are grown on plastic substratum under norm...

Epidermal growth factor receptor (EGFR) is a prototype receptor tyrosine kinase and serves as an oncogene in a variety of solid tumors. Its surface expression is dynamically regulated, and display of an activation-competent cell surface pool is an essential pre-requisite for cellular responses to EGF and other ligands, as well as for its oncogenic...

Precisely regulated cell proliferation is essential for embryonic development and for homeostasis in adult organs and tissues, whereas uncontrolled cell proliferation is a hallmark of cancer. We have identified the human orthologue of Drosophila Ecdysoneless (ECD) as a critical regulator of cell cycle progression and oncogenesis. ECD is overexpress...

Background and Significance: Calcium (Ca²⁺) is an essential signal transduction element involved in the regulation of several cellular activities such as gene transcription, proliferation and apoptosis. Endoplasmic Reticulum (ER) is the Ca²⁺ reservoir inside the cell that strictly orchestrate Ca²⁺ gradient across the Plasma Membrane(PM). Importantl...

Triple-negative and ErbB2+ breast cancer subtypes carry inherently poorer prognosis. The overall therapeutic response and survival are markedly lower in metastatic disease. This identification of novel pathways that collide with driver oncogenes to promote more aggressive disease and metastasis could help identify biomarkers for selection of patien...

Eps15 homology domain‐containing protein 4 (EHD4) regulates endocytic recycling. We previously reported that global EHD4 knockout (EHD4‐KO) mice have a higher urine flow and lower urine osmolality than wild‐type (WT) mice. Further, the diuretic phenotype in EHD4‐KO mice is associated with a reduced accumulation of aquaporin 2 (AQP2) in the apical m...

CHIP/STUB1 ubiquitin ligase is a negative co-chaperone for HSP90/HSC70, and its expression is reduced or lost in several cancers, including breast cancer. Using an extensive and well-annotated breast cancer tissue collection, we identified the loss of nuclear but not cytoplasmic CHIP to predict more aggressive tumorigenesis and shorter patient surv...

T cells use the endocytic pathway for key cell biological functions, including receptor turnover and maintenance of the immunological synapse. Some of the established players include the Rab GTPases, the SNARE complex proteins, and others, which function together with EPS-15 homology domain-containing (EHD) proteins in non-T cell systems. To date,...

The Eps15-homology domain-containing (EHD) protein family comprises 4 members that regulate endocytic recycling. Although the kidney expresses all 4 EHD proteins, their physiologic roles are largely unknown. This study focused on EHD4, which we found to be expressed differentially across nephron segments with the highest expression in the inner med...

Objective methodologies to discriminate tumor from normal tissue in biopsies and resection specimens are of great interest as complementary approaches to existing pathological diagnosis of tumors. In the present study, coherent anti-Stokes Raman scattering (CARS) spectroscopy was applied as an approach to discriminate resected tumor from normal mam...

The ADA3 (Alteration/Deficiency in Activation 3) protein is an essential adaptor component of several Lysine Acetyltransferase (KAT) complexes involved in chromatin modifications. Previously, we and others have demonstrated a crucial role of ADA3 in cell cycle progression and maintenance of genomic stability. Recently, we have shown that acetylatio...

The human apurinic/apyrimidinic endonuclease 1 (APE1) is a pleiotropic nuclear protein with roles in DNA base excision repair pathway as well as in regulation of transcription. Recently, the presence of extracellular plasma APE1 was reported in endotoxemic rats. However, the biological significance and the extracellular function of APE1 remain uncl...

The mammalian Ecdysoneless (ECD) is a highly-conserved ortholog of the Drosophila Ecd gene product whose mutations impair the synthesis of Ecdysone and produce cell-autonomous survival defects but mechanisms by which ECD functions are largely unknown. Here, we present evidence that ECD regulates endoplasmic reticulum (ER) stress response. ER stress...

Janus kinase 2 (JAK2) is a central kinase in hematopoietic stem/progenitor cells (HSPCs), and its uncontrolled activation is a prominent oncogenic driver of hematopoietic neoplasms. However, molecular mechanisms underlying the regulation of JAK2 have remained elusive. Here we report that the Casitas B-cell lymphoma (CBL) family E3 ubiquitin ligases...

Scientific Reports 6 : Article number: 20727 10.1038/srep20727 ; published online: 17 February 2016 ; updated: 23 March 2017 A reader alerted us of a potential error in Figure 12B and its accompanying Supplementary Figure 13B, since the indicated bands for GST fusion proteins did not correspond to the distinct expected sizes.

CBL and CBL-B ubiquitin ligases are negative regulators of tyrosine kinase signaling with established roles in the immune system. However, their physiological roles in epithelial tissues are unknown. Here we used the MMTV-Cre-mediated Cbl gene deletion on a Cbl-b-null background as well as a tamoxifen-inducible mammary stem cell (MaSC)-specific Cbl...

Mutations of the tyrosine kinase-directed ubiquitin ligase CBL cause myeloid leukemias, but the molecular determinants of the dominant leukemogenic activity of mutant CBL oncogenes are unclear. Here, we first define a gain of function attribute of the most common leukemia-associated CBL mutant, Y371H, by demonstrating its ability to increase prolif...

In-vitro self-renewal abilities of transformed K5+/K19- or K5+/K19+ cell lines. A, B and C Quantification of tumorspheres formed by vector or mp53/mRas/mPIK3CA gene combination over-expressing K5+/K19- and K5+/K19+ cells in different passages. Indicated cell lines were cultured in low-attachment plates in MEGM media for 3 weeks. Spheres ≥200μm were...

In-vitro transformation abilities of K5+/K19- and K5+/K19+ cells over-expressing mp53/mPIK3CA. A). Representative images (magnification 4X) of colonies from K5+/K19- and K5+/K19+ cells with vector or mp53/mPIK3CA oncogene combination, as assessed by anchorage independent growth assay. B) Quantification of colonies formed by different cells. Mean ±...

Differential EMT in mRas/mp53/mPIK3CA transformed K5+/K19- and K5+/K19+ cell lines. (A) Phase contrast images showing differences in EMT phenotype in transformed K5+/K19- (clone 62) or K5+/K19+ (clone 21) cells (magnification 10X). (B) Parental or transformed K5+/K19- or K5+/K19+ cells were analyzed by western blotting for the expression of EMT mar...

Janus Kinase 2 (JAK2) is the central tyrosine kinase in the signaling pathway of an array of hematopoietic receptors including thrombopoietin receptor (TPOR or MPL) in hematopoietic stem cells (HSCs) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in myeloid progenitors. While JAK2 plays an essential role in normal hematopoietic devel...

Breast cancer is characterized into different molecular subtypes, and each subtype is characterized by differential gene expression that are associated with distinct survival outcomes in patients. PIK3CA mutations are commonly associated with most breast cancer subtypes. More recently PIK3CA mutations have been shown to induce tumor heterogeneity a...

Background We have established the critical role of ADA3 as a coactivator of estrogen receptor (ER), as well as its role in cell cycle progression. Furthermore, we showed that ADA3 is predominantly nuclear in mammary epithelium, and in ER+, but is cytoplasmic in ER- breast cancers, the latter correlating with poor survival. However, the role of nuc...

Accumulation of BACE1 in dystrophic neurites surrounding amyloid deposits is a shared pathological feature in human Alzheimer's disease (AD) and transgenic mouse models. Several hypotheses have been proposed to explain the amyloid deposit-associated increase in BACE1 levels, and how this presynaptic elevation of BACE1 might contribute to amyloid pr...

The RNA polymerase II mediated transcription requires the higher degree structure of chromatin to be relieved so that general transcription machinery can access the DNA. The acetylation of DNA bound histones at specific loci is the major epigenetic modification by which opening of chromatin is achieved. HATs (Histone Acetyl Transferase) are the enz...

Alteration/Deficiency in Activation 3 (ADA3) is an essential component of specific HAT (Histone Acetyltransferase) complexes. We have previously shown that ADA3 is required for establishing global histone acetylation patterns and for normal cell cycle progression. Here, we report that these functional roles of ADA3 require its acetylation. We show...

CBL-family ubiquitin ligases are critical negative regulators of tyrosine kinase signaling, with a clear redundancy between CBL and CBL-B evident in the immune cell and hematopoietic stem cell studies. Since CBL and CBL-B are negative regulators of immune cell activation, elimination of their function to boost immune cell activities could be benefi...

Colony stimulating factor-1 receptor (CSF-1R), a receptor tyrosine kinase (RTK), is the master regulator of macrophage biology. CSF-1 can bind CSF-1R resulting in receptor activation and signalling essential for macrophage functions such as proliferation, differentiation, survival, polarization, phagocytosis, cytokine secretion, and motility. CSF-1...

Regulatory mechanisms that ensure effective antigen-specific responses by T-cells without evoking autoimmune disease are of great interest in basic and clinical immunology. While signaling through T-cell receptor (TCR) and positive and negative co-receptors have received great attention, mechanisms that control the dynamic traffic of such receptors...

Macrophage biology is regulated via receptor tyrosine kinase (RTK) CSF-1 receptor (CSF1R). Anomalous macrophage biology has been shown to be hallmark in diseases such as cancer and atherosclerosis. Although CSF1R signaling has been studied, little is known about the mechanisms which govern the endocytic trafficking of the receptor. EHD1 is known to...

C‐terminal Eps15 Homology Domain‐containing protein 4 (EHD4) regulates endocytic recycling but its function in the kidney is unknown. Previously we found that, despite similar water intake, Ehd4 −/− (EHD4‐KO) mice produced a higher volume of osmotically dilute urine compared to wild type (WT) mice, suggesting defective water handling in EHD4‐KO mic...

The human homolog of Drosophila ecdysoneless protein (ECD) is a p53 binding protein that stabilizes and enhances p53 functions. Homozygous deletion of mouse Ecd is early embryonic lethal and Ecd deletion delays G1-S cell cycle progression. Importantly, ECD directly interacts with the Rb tumor suppressor and competes with the E2F transcription facto...

Members of the four-member C-terminal EPS15-Homology Domain-containing (EHD) protein family play crucial roles in endocytic recycling of cell surface receptors from endosomes to the plasma membrane. In this study, we show that Ehd1 gene knockout in mice on a predominantly B6 background is embryonic lethal. Ehd1-null embryos die at mid-gestation wit...

Targeted delivery of anticancer drugs to tumor cells using monoclonal antibodies against oncogenic cell surface receptors is an emerging therapeutic strategy. These strategies include drugs directly conjugated to monoclonal antibodies through chemical linkers (Antibody-Drug Conjugates, ADCs) or those encapsulated within nanoparticles that in turn a...

Key Points SPRY2 is downregulated in CLL cells from patients with poor prognosis. SPRY2 is negative regulator of Syk-mediated BCR and MAPK-Erk signaling in CLL.

Ecdysoneless (ECD) is an evolutionarily-conserved protein whose germline deletion is embryonic lethal. Deletion of Ecd in cells causes cell cycle arrest which is rescued by exogenous ECD , demonstrating a requirement of ECD for normal mammalian cell cycle progression. However, the exact mechanism by which ECD regulates cell cycle is unknown. Here,...

Background: The mesolimbic dopamine system, composed primarily of dopaminergic neurons in the ventral tegmental area that project to striatal structures, is considered to be the key mediator of reinforcement-related mechanisms in the brain. Prompted by a genome-wide association meta-analysis implicating the Ras-specific guanine nucleotide-releasin...

Mutations of the tyrosine kinase-directed ubiquitin ligase CBL are associated with myeloid malignancies, yet the molecular mechanisms by which this tumor suppressor becomes a dominant oncogene to initiate the leukemogenic process are unclear. In this study, we used systematic mutagenesis to delineate the importance of the various protein-protein in...

Neuropilin-2 (NRP2) is a non-tyrosine kinase receptor frequently overexpressed in various malignancies where it has been implicated in promoting many protumorigenic behaviors, such as imparting therapeutic resistance to metastatic cancer cells. Here, we report a novel function of NRP2 as a regulator of endocytosis, which is enhanced in cancer cells...

The C-terminal Eps15 homology domain-containing (EHD) proteins play a key role in endocytic recycling, a fundamental cellular process that ensures the return of endocytosed membrane components and receptors back to the cell surface. To define the in vivo biological functions of EHD1, we have generated Ehd1 knockout mice and previously reported a re...

Alteration/Deficiency in Activation 3 (ADA3) is a conserved component of several transcriptional co-activator and histone acetyl transferase (HAT) complexes. Recently, we generated Ada3 knockout mice and demonstrated that deletion of Ada3 leads to early embryonic lethality. Use of Ada3FL/FL mouse embryonic fibroblasts (MEFs) with deletion of Ada3 u...

We previously showed that Eps15 homology domain-containing 1 (EHD1) interacts with ferlin proteins to regulate endocytic recycling. Myoblasts from Ehd1-null mice were found to have defective recycling, myoblast fusion, and consequently smaller muscles. When expressed in C2C12 cells, an ATPase dead-EHD1 was found to interfere with BIN1/amphiphysin 2...

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Breast cancer is classified in to different subtypes based on gene expression profiling. Significantly distinct subtypes present different outcome for patient survival, thus underscoring importance of understanding the role of precursor cell and genetic alterations in...

Objectives: Mutations in Cbl or Cbl-b gene occur in 10% of myeloproliferative disorder (MPD) patients and are associated with poor prognosis. Hematopoietic Cbl/Cbl-b double knockout (DKO) leads to a disease in mice phenotypically similar to human MPDs. The aim of this study was to evaluate the anti-MPD activity of a clinically safe drug, Fasudil,...

p53 and Notch-1 play important roles in breast cancer biology. Notch-1 inhibits p53 activity in cervical and breast cancer cells. Conversely, p53 inhibits Notch activity in T-cells but stimulates it in human keratinocytes. Notch co-activator MAML1 binds p53 and functions as a p53 co-activator. We studied the regulation of Notch signaling by p53 in...

The immunological synapse (IS) is a specialized membrane domain with localized display of T-cell receptor (TCR) in contact with a similar display of peptide-loaded MHC on antigen presenting cells (APCs). Aberrant IS function is linked to ineffective tumor killing and autoimmunity. Accumulating evidence indicates a key role of endocytic traffic in t...

Breast cancer is classified into different subtypes that are associated with different patient survival outcomes, underscoring the importance of understanding the role of precursor cell and genetic alterations in determining tumor subtypes. In this study, we evaluated the oncogenic phenotype of two distinct mammary stem/progenitor cell types design...

Proper trafficking of membrane-bound ion channels and transporters is requisite for normal cardiac function. Endosome-based protein trafficking of membrane bound ion channels and transporters in the heart is poorly understood, particularly in vivo. In fact, for select cardiac cell types such as atrial myocytes, virtually nothing is known regarding...

Cbl and Cbl-b are tyrosine kinase-directed RING finger type ubiquitin ligases (E3s) that negatively regulate cellular activation pathways. E3 activity-disrupting human Cbl mutations are associated with myeloproliferative disorders (MPD) that are reproduced in mice with Cbl RING finger mutant knock-in or hematopoietic Cbl and Cbl-b double knockout....

ErbB2-driven breast cancers constitute 20-25% of the cases diagnosed within the USA. The humanized anti-ErbB2 monoclonal antibody, Trastuzumab (Herceptin™; Genentech), with chemotherapy is the current standard of treatment. Novel agents and strategies continue to be explored, given the challenges posed by Trastuzumab-resistance development in most...

Abstract The mammalian ortholog of Drosophila ecdysoneless (Ecd) gene product regulates Rb-E2F interaction and is required for cell cycle progression. Ecd is overexpressed in breast cancer and its overexpression predicts shorter survival in patients with ErbB2-positive tumors. Here, we demonstrate Ecd knock down (KD) in human mammary epithelial cel...

Background Identification and characterization of molecular controls that regulate mammary stem and progenitor cell homeostasis are critical to our understanding of normal mammary gland development and its pathology.ResultsWe demonstrate that conditional knockout of Sox9 in the mouse mammary gland results in impaired postnatal development. In short...

Epidermal growth factor receptor (EGFR) controls a wide range of cellular processes, and aberrant EGFR signaling as a result of receptor overexpression and/or mutation occurs in many types of cancer. Tumor cells in non-small cell lung cancer (NSCLC) patients that harbor EGFR kinase domain mutations exhibit oncogene addiction to mutant EGFR, which c...