Category: Publications

Dr. Arturo Vegas Presents Research to Congressional Biomedical Research Caucus

November 27th, 2016 in Faculty, Outreach, Publications, Recognition, Research

Dr. Vegs PresentsOn October 5th, 2016 Dr. Arturo Vegas, who is a leader in the development of targeted therapies, discussed the recent progress to overcome challenges in the field including the development of automated insulin dosing, the production of mature insulin-producing cells from human stem cells, and new materials that can be used to prevent the rejection of transplanted insulin-producing tissue to the Coalition for the Life Sciences Congressional Biomedical Research Caucus.

Lynn Marquis, the Director of the Coalition for the Life Sciences Congressional Biomedical Research Caucus, invited Dr. Vegas to present his exciting research on Type 1 diabetes to a varied group of Congressional Representatives from across the country.

Type 1 diabetes, formally known as juvenile diabetes, is a disease characterized by the inability of patients to produce their own insulin hormone. It currently afflicts an estimated three million Americans. While a rigorous regimen of blood glucose monitoring coupled with daily injections of insulin remains the leading treatment, diabetics still suffer ill effects due to challenges with daily compliance and imperfect blood glucose control. The technologies Dr. Vegas is researching and discussed are bringing us closer than ever to mitigating this disease and improving the quality of life for these patients.

“The words of Sir Winston Churchill are applicable regarding the impact of their significant advances on a potential cure for diabetes: ‘This is not the end. It is not even the beginning of the end. But it is perhaps the end of the beginning.’” –Stock et al. Cell Stem Cell 18: 431-433. 2016

Watch his presentation here: “Are We Close to a Cure for Type 1 Diabetes?” – Arturo Vegas Presents to CBRC

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Dr. Malika Jeffries-EL, coauthor of a paper selected for the Journal of Materials Chemistry C Hot Papers

May 11th, 2016 in Malika, Publications, Recognition, Research, Uncategorized

BU Chemistry Professors are moving and shaking these days, with publications like this on being accepted into Journals such as the 2016 Journal of Materials Chemistry C Hot Papers.

The paper, whose lead author was Dr. Ramiro Chavez, a graduate student at BU in the lab of Malika Jeffries-EL, focuses on a structure–property investigation of a series of cross-conjugated molecules shows that their performance is dependent on both the nature of the substituents and their conjugation axis.

  Graphical abstract: Benzobisoxazole cruciforms: a tunable, cross-conjugated platform for the generation of deep blue OLED materials

For more information on the publication click here.

Jasti Carbon Nanohoop Research Featured in C&E News

August 2nd, 2012 in Front Page, Jasti, Ramesh, Publications

Professor Ramesh Jasti

Professor Ramesh Jasti

In a July 19 article, C&E News reported on the work of Professor Ramesh Jasti and his Group on carbon nano hoops. Cycloparaphenylenes (CPPs) or nanohoops are made from para-linked benzene rings. Stacking of CPPs could be the basis for preparing useful quantities of pure carbon nanotubes. However, CPPs are so  difficult to make that they are currently sold commercially for about $100 per milligram.  In a remarkable achievement, the Jasti Group have developed a new catalytic method that boosts the yields of eight- and 10-unit nanohoops by two orders of magnitude.  As reported in C&E News, this work has implications for nanoelectronics because armchair nanotubes, the type of carbon nanotubes that would be made by nanohoop stacking, are highly prized as conductive nanowires.

Ramesh Jasti joined the BU faculty in 2009.  The reported work is part of his laboratories goal of utilizing organic synthesis to probe the physics and theory of carbon nanostructures, with the ultimate goal of developing new applications in nanotechnology.  Prior to coming to BU, he was one of the first postdoctoral fellows at the Molecular Foundry—a US Department of Energy nanoscience facility at the Lawrence Berkeley National Laboratory.  As a highly interdisciplinary scientist, Professor Jasti also has appointments in the Materials Science and Engineering Division, as well as the Center for Nanoscience and Nanobiotechnology.

Jasti C&E News Figure

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Reinhard Research Provides Insights into HIV-1

May 14th, 2012 in Front Page, Publications, Reinhard, Björn, Uncategorized

Professor Bjoern Reinhard

Professor Bjoern Reinhard

Recently reported in PNAS, Bjoern Reinhard and his collaborator at the BU Medical School, Dr. Suryaram Gummuluru, have confirmed a unique HIV-1 DC attachment mechanism using lipoparticles with defined surface composition. The  mechanism is dependent on a host-cell–derived ligand, GM3, and is a unique example of pathogen mimicry of host-cell recognition pathways that drive virus capture and dissemination in vivo.   These insights provide the basis for the development of artificial virus nanoparticles with host-derived surface groups that inhibit the HIV-1 trans-dissemination pathway through dendritic cells. The virus parasite uses these dendritic cells to facilitate its dissemination, while avoiding recognition.

Citation: Puryear, et al., “HIV-1 incorporation of host-cell–derived glycosphingolipid GM3 allows for captureby mature dendritic cells”, Proc Natl Acad USA, 2012, 109 (19), 7475-7480.

Reinhard PNAS Fig 1

Gangliosides with α2–3 NeuNAc linkages are important for HIV-1 capture by mDCs. (A) Gag-eGFP VLPs were mock treated or treated with 0.5 units/μL α2–3, 2–6, 2–8 NA. (B) Gag-eGFP VLPs were derived from siRNA-treated HEK293T cells. NT, nontargeting; UGT8, galactosyl transferase; CERT, ceramide transfer protein; UGCG, glucosyltransferases, ST3, GM3 transferase. Capture of VLPs by mDCs was analyzed by FACS (A and B). Data are reported as percentage of eGFP+ mDCs normalized to NT-treated VLPs. (C and D) Ganglioside-deficient HIVLai was derived from HEK293T cells knocked down for NT, UGCG, or ST3. (C) Virions were labeled for p24gag (green) and GM3 (red). Representative fields are shown and the average mean fluorescent intensity (MFI) of GM3 normalized to p24gag ± SD is reported, *P < 0.001, one-way ANOVA with Dunnett’s multiple comparison. (D) Fold decrease of ganglioside-depleted HIVLai capture relative to NT-treated viruses by mDCs is reported. (E) Fold decrease in HIVLaiΔEnv virus capture treated with 0.5 units/μL α2–3, 2–6, 2–8 NA or α2–3-specific NA relative to mock-treated viruses by mDCs is reported. All capture assays represent averaged data from a minimum of three donors, ±SEM, one-sample t test, *P < 0.05, **P < 0.01, ***P < 0.001.

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Reinhard Article Among Ten Most Read in February

April 27th, 2012 in Front Page, Publications, Reinhard, Björn

Professor Bjoern Reinhard

Professor Bjoern Reinhard

The article by Bjoern Reinhard, “Molding the flow of light on the nanoscale: from vortex nanogears to phase-operated plasmonic machinery” (Nanoscale, 2012, 4, 76-90; DOI: 10.1039/C1NR11406A), was amongst the top ten accessed articles from the online version of Nanoscale in February 2012. Launched in 2009, Nanoscale is a new peer reviewed journal publishing experimental and theoretical work across the breadth of nanoscience and nanotechnology.

The Reinhard Group research focuses on new optical materials and their application to interrogate fundamental life processes. They explore the interface between nanotechnology and biological systems. For an overview of current research projects, please visit their group’s website.

Plasmonic nanolens as an internal vortex nanogear transmission. (a) Schematic of the self-similar Ag nanolens proposed in ref 72 (r1 = 45 nm, r2 = 15 nm, r3 = 5 nm, d1 = 9 nm, d2 = 3 nm, ambient index n = 1.0). (b and c) Electric field intensity distribution in the nanolens illuminated on- (b) and off-resonance (c) with the near-field intensity maximum of the nanolens. Far-field (d) and near-field intensity enhancement (e) spectra of the nanolens. (f) The amplitude of the Poynting vector and the phase of the Poynting vector in the x–z plane at the center of the nanolens narrower interparticle gap as a function of wavelength. (g and h) Poynting vector intensity distribution and powerflow around the nanolens off (g) and on (h) the peak intensity wavelength. (i) Schematic of the VNT generated in the nanolens at the peak intensity resonance. Light flux in each nanogear is looped through nanoparticles .

Plasmonic nanolens as an internal vortex nanogear transmission. (a) Schematic of the self-similar Ag nanolens proposed in ref 72 (r1 = 45 nm, r2 = 15 nm, r3 = 5 nm, d1 = 9 nm, d2 = 3 nm, ambient index n = 1.0). (b and c) Electric field intensity distribution in the nanolens illuminated on- (b) and off-resonance (c) with the near-field intensity maximum of the nanolens. Far-field (d) and near-field intensity enhancement (e) spectra of the nanolens. (f) The amplitude of the Poynting vector and the phase of the Poynting vector in the x–z plane at the center of the nanolens narrower interparticle gap as a function of wavelength. (g and h) Poynting vector intensity distribution and powerflow around the nanolens off (g) and on (h) the peak intensity wavelength. (i) Schematic of the VNT generated in the nanolens at the peak intensity resonance. Light flux in each nanogear is looped through nanoparticles .

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Collaborative Research Discovers New Approach in the Treatment of Liver Cancer

April 9th, 2012 in CMLD, Publications, Research, Schaus, Scott

Prof Scott Schaus

Professor Scott Schaus

Until now, there has been no effective, systemic treatment for liver cancer (hepatocellular carcinoma), the fifth most common cancer worldwide. Writing in the Proceedings of the National Academy of Science (PNAS), Professor Scott Schaus (Chemistry) and Professor Ulla Hansen (Biology and Molecular Biology, Cell Biology & Biochemistry) have reported their discovery of a new protein target for chemotherapy in the treatment of liver cancer — the transcription factor LSF. LSF occurs at high levels in the tumor tissue of patients with liver cancer and is known to promote the development of cancer (oncogenesis) in studies using laboratory rodents.

The co-investigators have identified small molecules that effectively inhibit LSF cellular activity, which in turn slows the growth of the cancer. In particular, they found that one such molecule, Factor Quinolinone Inhibitor 1 (FQI1), derived from a lead compound, inhibits the ability of LSF to bind DNA both in extracts (in vitro, as determined by electrophoretic mobility shift assays) and in cells. Consistent with inhibiting LSF activity, FQI1 also eliminates the ability of LSF to turn up transcription. While FQI1 quickly causes cell death in LSF-overexpressing cells, including liver cancer cells, healthy cells are unaffected by the treatment. This phenomenon has been called oncogene addiction, where tumor cells are “addicted” to the activity of an oncogenic factor for their survival, but normal cells can do without it. This characteristic is very encouraging for use
of such compounds clinically.

Structures of LSF inhibitors

Structures of LSF inhibitors

Following in vitro trials, the researchers tested the efficacy of FQI1 in inhibiting liver cancer tumor growth by injecting HCC cell lines into rodent models. FQI1 was observed to significantly inhibit tumor growth with no observable side effects (general tissue cytotoxicity). These dramatic findings support the further development of LSF inhibitors as a promising new chemotherapy treatment for liver cancer.

This work is featured as part of the series, “BU Takes on Cancer,” in BU Today (April 11, 2012).

 

Citation: T.J. Grant, J. A. Bishop, L.M. Christadore, G. Barot, H.G. Chin, S. Woodson, J. Kavouris, A. Siddiq, R. Gedler, X-N. Shen, J. Sherman, T. Meehan, K. Fitzgerald, S. Pradhan, L.A. Briggs, W.H. Andrews, D. Sarkar, S.E. Schaus, and U. Hansen, “Antiproliferative small-molecule inhibitors of transcription factor LSF reveal oncogene addiction to LSF in hepatocellular carcinoma,” Proc. Natl. Acad. Sci. U.S.A., March 20, 2012, Vol. 109, No. 12, 4503-4508.

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CMLD Researchers Publish Paper on “Remodeling” Natural Products in Nature Chemistry

November 7th, 2011 in Beeler, Aaron, CMLD, Front Page, Porco, John, Publications, Snyder, John

CMLD-BU researchers Bradley Balthaser, Meghan Maloney, Aaron Beeler, John Porco & John Snyder, in a paper published in the journal Nature Chemistry [23 OCTOBER 2011 | DOI: 10.1038/NCHEM.1178], present a new approach to accessing new, biorelevant structures by “remodeling” natural products. In this case, they demonstrate how the natural product derivative fumagillol can been remodeled to access a collection of new molecules using highly efficient chemical reactions.

a, Selective formation of perhydroisoindoles, perhydroisoquinolines or morpholinones with phenylalanine as a reaction partner: (i) phenylalanine (2.0 equiv.), M(OTf)n (50 mol%), DTBMP (1.5 equiv.), toluene, 60 °C; (ii) NaOH (2.0 M), tetrahydrofuran, room temperature, 6 h. DTBMP, 2,6-di-tert-butyl-4-methylpyridine; Phe, phenylalanine. b, Molecular models of phenylalanine-derived morpholinones 18 and 21.

a, Selective formation of perhydroisoindoles, perhydroisoquinolines or morpholinones with phenylalanine as a reaction partner: (i) phenylalanine (2.0 equiv.), M(OTf)n (50 mol%), DTBMP (1.5 equiv.), toluene, 60 °C; (ii) NaOH (2.0 M), tetrahydrofuran, room temperature, 6 h. DTBMP, 2,6-di-tert-butyl-4-methylpyridine; Phe, phenylalanine. b, Molecular models of phenylalanine-derived morpholinones 18 and 21.

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Drug Mechanism of Action Using Bioinformatic Pathway Analysis

August 3rd, 2011 in Faculty, Front Page, Graduate, Publications, Research, Schaus, Scott, Students

Lisa Christadore

Lisa Christadore

Professor Scott Schaus

Professor Scott Schaus

Professor Scott Schaus and Graduate Student Lisa Christadore are co-authors of:

Network-based prediction for sources of transcriptional dysregulation using latent pathway identification analysis

Published in PNAS in July 2011, the paper represents their collaborative work with researchers in the BU Department of Mathematics and Statistics, Professor Eric Kolaczyk and Graduate Student Lisa Pham.

It reports on the effectiveness of their novel method, latent pathway identification analysis (LPIA), in providing insights into systemic biological pathways and key cellular mechanisms that dictate disease states, drug response, and altered cellular function. The work was supported by NIH, NSF, and DOD.

Network-based prediction for sources of transcriptional dysregulation using latent pathway identification analysis.

Schematic illustration of the proposed LPIA method.

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Insights into Protein-Misfolding Diseases

January 20th, 2011 in Faculty, Front Page, Publications, Straub, John

Professor John Straub

Professor John Straub

The work of Professor John Straub and his collaborators at the University of Maryland, Dr. Govardhan Reddy and Professor Dave Thirumalai demonstrates that when aggregation occurs in aqueous solution between amyloid or prion peptides—which are associated with protein-misfolding diseases—a dry interface between the biomolecules forms in two different ways, suggesting how aggregation rates might differ substantially between proteins (Proc. Natl. Acad. Sci. USA, 107(50), 21459-21464, DOI: 10.1073/pnas.1008616107).

The work is highlighted in the December 2010 issue of C&E News.

Straub: Protein-Misfolding Diseases

Prion peptides in aqueous solution (left) aggregate to form a fibril with a dry interface (right) via an intermediate with trapped “water wires” (middle).

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Wang Research Featured in Journal of Chemical Physics and Honored at the ACS National Meeting

September 13th, 2010 in Faculty, Front Page, Publications, Research, Wang, Feng

Professor Feng Wang

Professor Feng Wang

The cover of the Aug. 28th, 2010 issue of the Journal of Chemical Physics, highlights a free-energy diagram calculated with a new enhanced sampling method developed by Professor Feng Wang and his Group (J. Chem. Phys. 113, 084101 {2010]). Their method mimics features of a coarse-grained simulation at the atomic scale.  Recent validations performed by the Wang Group indicate that this method can significantly accelerate the dynamics for peptide folding and lipid self-assembly without notably changing the free energy landscape.

Professor Wang received a Hewlett-Packard Outstanding Junior Faculty Award for presenting this work at the 240th ACS National Meeting. This prestigious award is given by the Division of Computers in Chemistry of the American Chemical Society, with financial sponsorship from Hewlett Packard. The division receives applications from across the country and the award is highly competitive, with submissions by many excellent tenure-track faculty members. Winners are selected based on the novelty and potential impact of the applicant’s research program.

Professor Wang is currently working on coupling his novel approach with replica exchange molecular dynamics for enhanced sampling study, which is an exciting advance that could have a significant impact on the rapidly growing field of coarse-grained modeling.
Wang JCP Cover

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