 Tolias, Peter |
Academic Appointments: Dean, School of Natural and Behavioral Sciences, Brooklyn College, The City University of New York Degree Research Focus: My research team has focused on understanding the biochemistry of the Mitogen Activated Protein Kinase (MAPK) Signaling pathway and its role in cancer by developing and using drugs that can therapeutically modulate this biochemical pathway. The signaling that occurs within this pathway is extremely important as it controls many essential cellular functions such as cytoskeleton organization, aging and programed cell death, calcium signaling, trafficking of vesicles, and cellular proliferation/cell division. Proliferation of cells is a critical component of the MAPK pathway because when perturbed leads to many different types of solid tumors as well as blood cancers. To date, only two proteins, BRAF and MEK. that function in the MAPK pathway have been successful targeted with available FDA approved drugs. The problem with all currently approved drugs against these two targets is that patients develop resistance to the therapeutic effects of these drugs within two years and the caner returns, hence the need to develop new drugs against other targets in the MAPK pathway. At the top of the MAPK pathway are the products of the RAS gene which are among the highest priority drug targets in oncology. This gene is mutated, causing it to be hyperactive, in 30% of all human tumors including 90% of pancreatic, 45% of colon and 35% of lung cancers. Cancers with KRAS mutations are aggressive and respond poorly to standard untargeted chemotherapies. We have used computational modeling (supercomputing) of the mutated KRAS protein based on published X-ray crystallography data to determine areas that a drug can possibly bind as well as computational chemistry of compounds developed by others that have failed to effectively modulate the pathway. This metanalysis has led us to many new ideas of how to develop new candidate compounds. We then used medicinal organic chemistry to develop these new drug candidates against KRAS and proceeded to accesses them in biochemical assays. After numerous failures, a compound was synthesized with low but reproducible (in triplicate) biochemical inhibition (12%) of the hyperactive KRAS G12C mutant. We have also designed and synthesized a novel analogue of this compound in an effort to significantly enhance its potency. Computational modeling (supercomputing) of the mutated KRAS protein was also used based on published X-ray crystallography data to determine areas that a drug can possibly bind as well as computational chemistry of compounds developed by others that have failed to effectively modulate the pathway. This metanalysis has led us to many new ideas of how to develop new candidate compounds. We then used medicinal organic chemistry to develop these new drug candidates against KRAS and proceeded to accesses them in biochemical assays. After numerous failures, a compound was synthesized with low but reproducible (in triplicate) biochemical inhibition (12%) of the hyperactive KRAS G12C mutant. We have also designed and synthesized a novel analogue of this compound in an effort to significantly enhance its potency. A second target that we have pursued is the SOS protein which physically interacts with RAS and controls it’s GTPase activity and subsequent signaling. We studied the 3D X-ray structure of this interaction from publicly available data banks and identified a contact point that had a groove in SOS that we believed may offer a new target site to develop compounds that would inhibit the interaction in biochemical assays. We then proceeded to use computational modeling on a supercomputer and identified theoretical compounds that fit in this groove out of 11 million possible structures using high throughput docking at this junction site. Three of these compounds (out of the 103 that were identified by computational modeling) were confirmed biochemically with low micromolar potency and share a common scaffold. We are currently designing and synthesizing novel analogues of these compounds to significantly enhance their potency. Our third target in the MAPK pathway is ERK which is the last key protein involved in the signaling cascade. A drug against ERK would create a new effective first line treatment for melanoma, colon and pancreatic cancer and new hope for patients with BRAF and MEK resistant tumors. We have spent most of our effort on this target and have been able to push our progress to a significant milestone. Our approach was similar to what was done in the RAS project described earlier in that we used computational modeling (supercomputing) of the ERK protein based on published X-ray crystallography data to determine areas that a drug can possibly bind as well as computational chemistry of compounds developed by others that have failed to effectively modulate the pathway. We then used medicinal chemistry in an attempt to develop a novel, potent, selective, orally efficacious ERK inhibitor. Fortuitously, one of the candidate compounds that we synthesized early in our efforts was able to inhibit ERK in a biochemical assay with excellent potency. Through multiple cycles of computational refinement, organic chemistry synthesis and biochemical assessment, we have identified a very potent compound in the low nanomolar range Selected Publications
Patents
Grants over the last 5 years
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 Greer, Alec |
Academic Appointments: Professor of Chemistry, Brooklyn College of CUNY Degrees: BS California State University, Chico; Ph.D. Chemistry, U. Wyoming Research Focus: Our group utilizes both experimental and theoretical methods to research fundamental aspects of organic chemistry and photochemistry. We are eager to accept researchers from various backgrounds, including nanotechnology, biochemistry, and even engineering. Our main focus is controlling and amplifying the production of reactive oxygen species. Our current projects involve organic oxidation mechanisms, visible-light photosensitization, secondary photosensitization, latent reactions following photooxidation, and photochemical-device development. One research area involves the use of fiber optics combined with sensitizer drugs for the production and precise delivery of singlet oxygen to eradicate cancer cells. This technique is referred to as “point-source” photodynamic therapy (i.e., PSPDT), delivers oxygen and red diode laser light through a device tip directed at the tumor site. This device helps avoid damage to healthy cells by focusing the sensitizer drugs and laser light within the tumor site. We also study the interfacial behavior of reactive oxygen species, including radicals at nanoparticle interfaces, and also the delivery of alkoxy radicals and singlet oxygen both as individual or tandem disinfectants. As mentioned above, secondary reactions are of interest to us. For example, the deconvolution of competitive light and dark processes is us offering insight into a priming mechanisms, including singlet oxygen priming as distinct from photodynamic priming. We are also using density functional theory and ab initio calculations which guide and deepen our understanding of experiments. Our work is currently funded by the National Science Foundation. Selected Publications C. C. Tonon; Xu, Q.; Ghosh, G.; S Ashraf; A. Nara de Sousa Rastelli; T. Hasan; A. Greer; A. L. Lyons “Evaluation of Photosensitizer-Containing Superhydrophobic Surfaces for the Antibacterial Treatment of Periodontal Biofilms” J. Photochem. Photobiol. B 2022, 112458. B. Malek; W. Lu; P. P. Mohapatra; N. Walalawela(a); S. Jabeen(a); J. Liu; A. Greer “Probing the Transition State-to-Intermediate Continuum: Mechanistic Distinction Between a Dry vs Wet Perepoxide in the Singlet Oxygen ‘Ene’ Reaction at the Air-Water Interface” Langmuir 2022, 38, 6036-6048. E. M. Greer; V. Siev; A. Segal; A. Greer; C. Doubleday “Computational Evidence for Tunneling and a Hidden Intermediate in the Biosynthesis of Tetrahydrocannabinol” J. Am. Chem. Soc. 2022, 144, 7646-7656. Belh, S. J.(a); Ghosh, G.; Greer, A. “Surface-Radical Mobility Test by a Self-Sorting Mechanism: Symmetrical Product upon Recombination (SPR)” J. Phys. Chem. B 2021, 125, 4212-4220. A. M. Durantini; A. Greer “Interparticle Delivery and Detection of Volatile Singlet Oxygen at Air/solid Interfaces” Environ. Sci. Technol. 2021, 55, 3559-3567. R. M. O’Connor(c); A. Greer “How Tryptophan Oxidation Arises by ‘Dark’ Photoreactions from Chemiexcited Triplet Acetone” Photochem. Photobiol. 2021, 97, 456-459. A. M. Durantini; P. P. Mohapatra; M. Ashaque(c); M. E. Zatoulovski(c); M. M. Kim; K. A. Cengel; T. M. Busch; T. C. Zhu; A. Greer “Photooxidative Vulnerability to Intralipid in Photodynamic Therapy” In Periodical Reports in Photochemistry of the Royal Society of Chemistry; Protti, S.; Raviola, C. Eds.; Cambridge, UK 2021, Vol. 48, pp. 411-422. M. J. Sosa; M. N. Urrutia; P. L. Schilardi; M. I. Quindt; S. Bonesi; D. Denburg; M. Vignoni; A. Greer;E. M. Greer; A. H. Thomas “Mono– and Bis-Alkylated Lumazine Sensitizers: Synthetic, Molecular Orbital Theory, Nucleophilic Index, and Photochemical Studies” Photochem. Photobiol. 2021, 97, 80-90. J. Robinson-Duggon; N. Pizarro; G. Gunther; D. Zúñiga-Núñez; A. M. Edwards; A. Greer; D. Fuentealba “Fatty Acid Conjugates of Toluidine Blue O as Amphiphilic Photosensitizers: Synthesis, Solubility, Photophysics, and Photochemical Properties” Photochem. Photobiol. 2021, 97, 71-79. Matikonda, S. S.; Helmerich, D. A.; Meub, M.; Beliu, G.; Kollmannsberger, P.; Greer, A.; Sauer, M.; Schnermann, M. J. “Defining the Basis of Cyanine Phototruncation Enables a New Approach to Single Molecule Localization Microscopy” ACS Cent. Sci. 2021, 7, 1144-1155. Highlighted in C&E News. M. S. Oliveira; G. Chorociejus; J. P. F. Angeli; G. M. V. V. Safadi; G. L. B. Aquino; G. E. Ronstein; L. F. Barbosa; M. C. Oliveira; M. H. G. Medeiros; A. Greer; P. Di Mascio “Heck Reaction Synthesis of Anthracene and Naphthalene Derivatives as Traps and Clean Chemical Sources of Singlet Molecular Oxygen in Biological Systems” Photochem. Photobiol. Sci. 2020, 19, 1590-1602. O. Turque(a); A. Greer; O. R. Wauchope “Synthetic Feasibility of Oxygen-driven Photoisomerizations of Alkenes and Polyenes” Org. Biomol. Chem. 2020, 18, 9181-9190. S. Jabeen(a); M. Farag(c); B. Malek(b); R. Choudhury; A. Greer A Singlet Oxygen Priming Mechanism: Disentangling of Photooxidative and Downstream Dark Effects. J. Org. Chem. 2020, 85, 12505-12513. Ortel; S. Jabeen; A. Greer “Adjuvants that Empower the Action of Photodynamic Therapy” Photochem. Photobiol.2020, 96, 725-727. Belh, S. J.; Walalawela, N.; Lekhtman,; Greer, A. “Dark-binding Process Relevant to Preventing Photooxidative Damage: Conformation Dependent Light and Dark Mechanisms by a Dual-functioning Diketone” ACS Omega 2019, 4, 22623-22631. Walalawela; A. Greer “Heterogeneous Photocatalytic Deperoxidation with UV and Visible Light” J. Phys. Org. Chem.2018, e3807. Malek; W. Fang; I. Abramova; N. Walalawela; A. A. Ghogare; A. Greer “Ene Reactions of Singlet Oxygen at the Air-Water Interface” J. Org. Chem. 2016, 81, 6395-6401. A. Ghogare; A. Greer “Using Singlet Oxygen to Synthesize Natural Products and Drugs” Chem. Rev. 2016, 116, 9994-10034. [(a) Ph.D. student; (b) MS student; (c) undergraduate student; (d) research assistant at Brooklyn College]
Lyons, A.M.; Greer, A.; Xu, Q.F., Singlet Oxygen Generating Device for Selective Destruction of Pathogens, US patent application No. 15/729005 Publication No. 20180099063, published 4/12/2018.
External Federal Funding NSF Single Investigator Award, 2022-2025 Mechanistic Organic Photochemistry: Dark Processes and Toxicity Priming NSF STTR Phase I Award, 2021-2022, (for our company SingletO2 Therapeutics LLC with co-PI Marc Hodes, Tufts University) Safe Disinfection and Oxygen-Level Enrichment in Recirculating Aquaculture Systems (RAS) Using Singlet Oxygen NSF Single Investigator Award, 2019-2022, Multiphase-Separation and Control of Serially Produced Reactive Oxygen NIH SBIR Phase II Award, 2019-2022, (for our company SingletO2 Therapeutics LLC) 3D-Printed Superhydrophobic-Tipped Optical Fiber for Targeted Periodontal Photodynamic Therapy
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 Gallicchio, Emilio |
Academic Appointments: Associate Professor (Sept. 2020), Chemistry Department, Brooklyn College, The City University of New York Degree(s) Ph.D. Chemical Physics (1996), Columbia University, New York, NY Research Focus: My background is in statistical thermodynamic theory and computational modeling. My laboratory is primarily involved in the development and application of molecular computational models of protein-drug binding and macromolecular molecular recognition phenomena. The overall aim of the research is to deploy sophisticated molecular theories, efficient algorithms, and powerful computers to characterize fundamental chemical and biological mechanisms and work with colleagues to help address human health issues. The specific application area we are currently targeting is the computational screening of potential drugs against protein receptors using massive atomistic computer simulations and accurate free energy models. Computer models are nowadays an important and established component of modern and interdisciplinary structure-based drug discovery programs. The advanced molecular dynamics-based binding free energy methods that we target, in particular, are attractive because they can yield estimates of binding constants useful for ranking the inhibitory potency of drug candidates and for direct comparison to binding affinity measurements. Computational studies of this kind yield valuable information about the energetic, structural, and dynamical behavior of drug-receptor complexes to complement medicinal chemistry efforts. Our research is intrinsically collaborative and interdisciplinary. As illustrated by the published works below, we regularly partner with medicinal chemistry laboratories to increase the chance of success of drug discovery programs against viral infections, cancer, and drug addiction among others. Selected Recent Publications
Grants over the last 5 years Emilio Gallicchio, PI
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 Torrente, Mariana |
Academic Appointments: Assistant Professor, Chemistry Department, Brooklyn College, The City University of New York Degree(s) NIH IRACDA Postdoctoral Fellow, University of Pennsylvania School of Medicine, Philadelphia, PA Research Focus: Our research involves epigenetics, proteomics and protein homeostasis. In particular, we are focused on the role of histone modifications in amyotrophic lateral sclerosis (ALS). ALS is a progressive and fatal neurodegenerative disease. Both familial and sporadic ALS produce similar symptoms; familial ALS represents 5-10% of cases. Familial ALS has been linked to a multitude of genes. How can so many genes produce the same symptomatology? We hypothesize that epigenetic mechanisms—namely histone modifications—play a pivotal role in ALS. Interestingly, a growing body of epidemiologic data suggests that neurodegenerative diseases occur less frequently in cancer survivors, and vice versa. We will study how disruptions in protein homeostasis could lead to cancer processes, and explore the overlapping aspects of neurodegenerative disease and cancer to develop strategies that could prevent both diseases. Selected Publications Bennett SA, Cobos SN, Meykler M§ , Fallah M§ , Rana N§ , Chen K and Torrente MP, Characterizing Histone Post-Translational Modification Alterations In Yeast Neurodegenerative Proteinopathy Models. Journal of Visualized Experiments, 2019, Mar 24;(145). DOI: 10.3791/59104 PMID: 30958470.§Undergraduate co-author(s) ^Corresponding author Bennett SA, Tanaz R, Cobos SN, and Torrente MP, Epigenetics in Amyotrophic Lateral Sclerosis: A Role for Histone Post-Translational Modifications in Neurodegenerative Disease. Translational Research. 2019 Feb; 204:19-30. DOI: 10.1016/j.trsl.2018.10.002. PMID: 30391475 PMCID: PMC6331271 Corresponding author Cobos SN, Bennett SA and Torrente MP, The Impact of Histone Post-translational Modifications in Neurodegenerative Disease. Biochim Biophys Acta Molecular Basis of Disease. 2018 Oct 20, pii: S0925-4439(18)30396-X. DOI: 10.1016/j.bbadis.2018.10.019. PMID: 30352259 ^Corresponding author Chen K, Bennett SA, Rana N§, Yosuf H§ , Said M§, Taaseen S§, Meltser SM§, Mendo N§ and Torrente MP, Distinct Histone Post-Translational Modifications Are Connected To Neurodegenerative Disease Proteinopathies. ACS Chemical Neuroscience, 2018, Apr 18;9(4):838-848. PMID: 29243911 PMCID: PMC5906139 DOI: 10.1021/acschemneuro.7b00297. §Undergraduate coauthor(s) ^Corresponding author Tariq A, Lin J, Noll MM§, Torrente MP, Mack KL, Hernandez Murillo O§, Jackrel ME, Shorter J. Potentiating Hsp104 activity via phosphomimetic mutations in the middle domain. FEMS Yeast Research. 2018 Aug 1;18(5). PMID: 29788207 DOI: 10.1093/femsyr/foy042. §Undergraduate coauthor(s) Gates SN, Yokom AL, Lin J, Jackrel ME, Rizo AN, Kendsersky NM, Buell CE§, Sweeny EA, Chuang E, Torrente MP, Mack KL, Su M, Shorter J and Southworth DR. Ratchet-like polypeptide translocation mechanism of the Hsp104 disaggregase. Science, 2017 Jul 21;357(6348):273-279. PMID: 28619716 PMCID: PMC5770238 DOI: 10.1126/science.aan1052 §Undergraduate co-author(s) Torrente MP, Chuang E, Noll MM §, Jackrel ME, Go MS, and Shorter J. Mechanistic Insights Into Hsp104 Potentiation. Journal of Biological Chemistry. 2016 Mar 4;291(10):5101-15 PMID: 26747608 PMCID: PMC4777845 DOI: 10.1074/jbc.M115.707976 §Undergraduate co-author(s) Grants over the last 5 years Ongoing Research Support National Institutes of Health The City University of New York Research Foundation of CUNY, The City University of New York Research Foundation of CUNY, The City University of New York
Completed Research Support Research Foundation of CUNY, The City University of New York Research Foundation of CUNY, The City University of New York
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 Singh, Shaneen |
Academic Appointments: Associate Professor, Department of Biology, Brooklyn College, The City University of New York Degrees: Ph.D. (Biotechnology), Thapar Institute of Engineering and technology, India Research Focus: The research focus of my lab is the application of computational approaches to gain insight into cellular signal transduction pathways, and the normal and aberrant functioning of proteins and protein domains. A novel feature of our approach is the integration of bioinformatics tools to analyze genomic and proteomic data with detailed computational analysis of the physical interactions. The computational models that we derive provide novel insights into the molecular basis of the formation and regulation of complexes and, thus, allow us to suggest rational and experimentally testable predictions as to their function. Overall, my lab has extensive expertise in the analysis of protein sequences and structures and is heavily involved in expanding our research to relevant cancer biology questions that encompass several new proteins/protein domains. The current cancer-related projects in the lab involving key protein players in oncogenesis include the interaction of nucleolin with different RNA species, computational characterization of the protein-protein interactions of the NEK family of proteins, protein-protein interactions of p27, and the membrane-protein interactions of the GAB family of proteins. Selected Publications: Barreto C, Silva A, Wiech E, Lopez A, San A, Singh S. (2022) Proteomic Tools for the Analysis of Cytoskeleton Proteins. Methods Mol Biol. 2022;2364:363-425. doi: 10.1007/978-1-0716-1661-1_19. PMID: 34542864. 2022 Jalali, S., Yang Y., Mahmoudinobar F., Singh, S.M, Nilsson, B., and Dias, C. (2022) Using large-scale and long-time all-atom simulations to study the aggregation of amphipathic peptides into amyloid-like fibrils. Journal of Molecular Liquids 347, 118283 Philip J, Örd M, Silva A, Singh S, Diffley JF, Remus D, Loog M, Ikui AE. (2022) Cdc6 is sequentially regulated by PP2A-Cdc55, Cdc14, and Sic1 for origin licensing in S. cerevisiae. Elife. 2022 Feb 10;11. doi: 10.7554/eLife.74437. PubMed PMID: 35142288; PubMed Central PMCID: PMC8830886. San A, Palmieri D, Saxena A, Singh S. (2022) In silico study predicts a key role of RNA-binding domains 3 and 4 in nucleolin-miRNA interactions. Proteins. 2022 May 5;. doi: 10.1002/prot.26355. [Epub ahead of print] PubMed PMID: 35514080. Murph, M., Singh, S., Schvarzstein, M. (2021) The Centrosomal Swiss Army Knife: A combined in silico and in vivo approach to the structure-function annotation of SPD-2 provides mechanistic insight into its functional diversity. Cell Cyle (In press; preprint available from bioRxiv 2021.04.22.441031) M Scarpati, Y Qi, S Govind, S Singh. (2019) A combined computational strategy of sequence and structural analysis predicts the existence of a functional eicosanoid pathway in Drosophila melanogaster. PloS one 14 (2), e0211897 [PMID: 30753230] VR Aitbakieva, R Ahmad, S Singh, AV Domashevskiy (2019) Inhibition of ricin A-chain (RTA) catalytic activity by a viral genome-linked protein (VPg) Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics 1867(6):645-653 [PMID: 30822539] Heavner, M.E., Ramroop, J., Gueguen, G., Ramrattan, G., Dolios, G., Scarpati, M., Kwiat, J., Bhattacharya, S., Wang, R., Singh, S., Govind, S. (2017) Novel Organelles with Elements of Bacterial and Eukaryotic Secretion Systems Weaponize Parasites of Drosophila. Current Biology 27, 2869-2877. [PMID: 28889977]
Grants over the last 5 years: PSC-CUNY. An in silico approach to decipher the mechanism of Cdc6 interactions with key interaction partners. (2022-2023) Tow Research and Creativity Grant. In silico study predicts a key role of RNA-binding domains 3 and 4 in Nucleolin-miRNA interactions. (2022) PSC-CUNY. Building a Nek10 interactome: A cancer-focused computational approach to map Nek10’s interacting protein partners. S. Singh. 1 year (2021-2022) In silico modeling of p27Kip1 with the Brk SH3 domain and variants to develop a p27drug candidate for treatment in cancer. Concarlo Holdings LLC., 1 year (2018-2019) PSC-CUNY Traditional A : Role of the Gab family pleckstrin homology domains in cancer: A computational study. 1 yr (2018-2019)
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 Schvarzstein, Mara |
Academic Appointments: Assistant Professor, Biology Department, Brooklyn College, The City University of New York Degrees Postdoctoral Scholar (Developmental Biology and Genetics), Stanford University, CA, USA Research Focus Our research focuses on uncovering causes and consequences of inheriting abnormal numbers of chromosomes. Polyploidy, the condition of inheriting more than the normal two copies of the entire genetic material present in a cell, is a key driving force of cancer development (Ganem et al. 2007). In particular tetraploidy (i.e. containing four copies of the entire genetic material) elevates the number of chromosomes lost and gained which results in the production of a variety of cells with structural and numerical aberrations of chromosomes (aneuploid cells). This assortment of aneuploid cells apparently confers oncogenic potential. Despite its importance in promoting cancer, little is known about how tetraploidy potentiates cancer development. My laboratory’s research program is aimed at both understanding how cells become polyploid or aneuploid and uncovering the molecular and cellular consequences of these chromosomal aberrations. We combine molecular genetics and genomic approaches with cell biological and biochemical techniques in the well-established model organism C. elegans. C. elegans is a very small transparent roundworm commonly used as a prototype for studying human diseases because it has many functional gene counterparts in humans. We recently established a new methodology to generate tetraploid C. elegans strains from any genetic background to explore the consequences of polyploidization and how tetraploidy facilitates aneuploidy. This is the only entirely tetraploid animal laboratory model system that is both viable and fertile. Using this unique system we are also studying how the cooperative behavior of chromosomes and the machinery (centrosomes and microtubules) that helps partition them during cell division ensure accurate chromosome inheritance. In addition, we are investigating the immediate and long-term consequences of the inheritance of abnormal number of chromosomes (aneuploidy and polyploidy). Selected Publications (*corresponding senior author, #graduate student author and &undergraduate student authors) Katherine Rivera Gomez# and Mara Schvarzstein*. (2018). Immobilization nematodes for live imaging using an agarose pad produced with a Vinyl Record. microPublication Biology. https://doi.org/10.17912/QG0J-VT85. Erlyana K. Clarke&, Katherine A. Rivera Gomez#, Zaki Mustachi&, Mikaela C. Murph&, Mara Schvarzstein*. (2018). Manipulation of Ploidy in Caenorhabditis elegans. JoVe issue 133 (DOI:10.3791/57296). Baptiste Roelens, Mara Schvarzstein*, and Anne M. Villeneuve*. (2015). Manipulation of karyotype in Caenorhabditis elegans reveals multiple inputs driving pairwise chromosome synapsis during meiosis. Genetics 201(4):1363-79. Schvarzstein M, Pattabiraman D, Libuda DE, Ramadugu A, Tam A, Martinez-Perez E, Rolelens B, Zawadzki KA, Yokoo R, Rosu S, Severson AF, Meyer BJ, Nabeshima K, Villeneuve AM. (2014). DNA Helicase HIM-6/BLM Both Promotes MutS-Dependent Crossovers and Antagonizes MutS-Independent Inter-Homolog Associations During Caenorhabditis elegans Meiosis. Genetics 114.161513. Schvarzstein M*, Pattabiraman D, Bembenek J and Villeneuve AM*. (2013). Meiotic HORMA domain proteins prevent untimely centriole disengagement during C. elegans spermatocyte meiosis. PNAS 110 (10) E898–E907. Schvarzstein M, Wignall SM and Villeneuve AM. (2010). Coordinating cohesion, co-orientation and congression during meiosis: Lessons from holocentric chromosomes. Genes Dev. 24(3): 219-28.
Grants and awards over the last 5 years Schvarzstein (PI): NIH SC2 GRANT1191484864 “Regulation of Chromosome and Centrosome Inheritance” PSC-CUNY Enhanced Research Award 62784-00 50 “Causes and consequences of whole animal polyploidization”, City University of New York PSC-CUNY Award B. TRADB-46-113 “Mechanisms by which HORMA proteins regulate chromosome and centrosome inheritance”, City University of New York Trainee-organized symposia grant PI: “Worms, evolution, & collaboration”, Genetics society of America” Scientific Meeting Grant EA299: Organizer of the Second North American Polyploidy Meeting at MDIBL, ME, USA. The Company of Biologists Student Technology Fund, Brooklyn College Rapid Response Honorarium, Wolfe Institute for the Humanities awarded to M.S. (for lectures on COVID19 genetics and evolution) Society for Developmental Biology Travel Award for M.S Plenary Talk Presentation “Causes and consequences of polyploidization”. |
 Saxena, Anjana |
Academic Appointments: 2021-present: Professor and Chairperson, Biology, Brooklyn College (CUNY) Degrees: BS Microbiology-Biochemistry Mumbai University, India Research Focus: Our major research focus is to understand how nucleolar stress factors (NSFs) that are RNA-binding proteins (RBPs) regulate gene expression and control cellular fate (survival, cell death or senescence). We are dissecting novel mechanistic role of stress responsive RBPs, in regulating gene expression during the DNA damage response (DDR), infection and tumorigenesis. In recent years we have expanded our research goals encompassing different diseases (e.g., different types of cancer including pancreatic, triple-negative breast cancer, colorectal and prostate cancers, diabetes & liver diseases). We focus on few major emerging research areas to understand: (i) Interplay between RBPs and their target RNA species that promotes cancer progression, (ii) epigenetic mechanisms that influence gestational diabetes, (iii) how the resident liver microbiome, the gut-microbiome and their metabolites, affect cellular immunity in carcinogenesis with host’s immune response that triggers inflammaging (low grade inflammation that characterizing aging). Selected Publications (up to 5): *Corresponding author, aPhD, bMA in Saxena’s lab denoted.
Patent: Patent US20040248190: “Compositions and kits for differential diagnosis of hydatidiform moles and methods of using the same”. Tycko B., Thaker H. and Saxena, A, 2004. Grants over the last 5 years: NIH/NIA R01 AG068857 08/15/2020-04/30/2025 NSF, RCN-UBE-Incubator Saxena (PI) 10/1/2022-9/30/22 The CUNY Enhanced Mechanism (ENHC-51-122), 07/2020-06/2021 The CUNY Interdisciplinary Research Grant (CIRG) Program 06/2018-06/2020 (no cost extension) Sackler Institute for Nutrition Research Grant (NYAS) 6/1/17-2/28/19 CUNY Student Technology Fee (STF): to purchase Odyssey Fc DNA and protein imager (2018)
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 Lipke, Peter N. |
Academic Appointments: Professor of Biology, Brooklyn College CUNY Degrees: BS Chemistry, U. Chicago; PhD Biochemistry, U. California Berkeley Research Focus: The Lipke has lab long been involved in research that is related to candidiasis and other fungal diseases, which are a cause of morbidity and mortality in a large number of cancer victims. His research interests include structure and function of cell adhesion proteins that mediate pathogen-host interactions and biofilm formation. His extensive work with collaborators in biophysics and medicine, highlights functional amyloids at the cell surface activating cell adhesion, and are potential targets for antifungal drugs. Biofilm formation has been shown to be a factor in the hosting of cancer-causing vectors linked to colon cancer and prostate cancer. Our recent work shows that fungal surface amyloids bind the innate Pattern Recognition Receptor SAP, and this binding leads to induction of an anti-inflammatory response, potentially dampening immune responses to tumors as well. In addition, Dr. Saxena’s recent work shows centrality of fungal infections in pancreatic cancers. Thus, fungal dysbiosis has a key role in cancer development and co-morbidity, so every cancer center therefore has the infectious disease unit that operates to manage fungal pathogenesis in cancer patients. Selected Publications (up to 5), h value = 41
Patents: Jackson, D.N., Kennelly, E., and P.N. Lipke. Method of preventing biofilm formation. Lipke, P. and U. Edupuganthi. Process for increased yeast biomass. Grants over the last 5 years NIH R01 GM098616 A Role for Amyloids in Force-Dependent Activation Of Cell Adhesion (PI/PD Lipke) 6/1/2012-3/31/2017 $1,390,000 Biothera, Inc. Proprietary Strain Production (PI/PD Lipke) 5/16/2011 – 11/30/2015 $775,000
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 Jiang, Xinyin |
Academic Appointments Associate Professor, Department of Health and Nutrition Sciences, Brooklyn College Degrees PhD in Nutrition (05/2013 at Cornell University) Research Focus My research is focused on nutrients involved in one carbon metabolism, such as choline, betaine, folate and vitamin B12, which affect various aspects of metabolic functions. My research group currently conducts mammalian cell culture, animal and human studies to assess the influence of choline intake during pregnancy on epigenetic programing and metabolic imprinting of offspring health. We are also interested in the interaction between one carbon metabolism and pathogenesis of diabetes, non-alcoholic fatty liver diseases, and cancer. Selected Publications
Patents: none
National Institutes of Health SCORE3 PSC-CUNY Enhance Egg Nutrition Center Research Grant, American Egg Board, USDA National Institutes of Health SCORE2 CUNY Interdisciplinary Research Grant Program New York Academy of Sciences Research Award PSC-CUNY Enhance
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 Gibney, Brian R. |
Academic Appointments: Professor, Chemistry Department, Brooklyn College, The City University of New York Degree(s) and awards E. Ann Nalley Regional Award for Volunteer Service to the American Chemical Society, 2020 Research Focus: The Gibney laboratory is focused on developing the nascent field of de novo metalloprotein design as a constructive methodology to delineate the fundamental engineering of metalloproteins, and to utilize their distinct chemistry for therapeutic use. Currently, we are delineating the role(s) of zinc ions in controlling gene expression in human cancer via the zinc finger proteins (ZFPs). Our investigative tools center on measuring the thermodynamics of metal-peptide and metal-protein equilibria. Our near-term goal is to provide the basis for improvements in the computational design of metalloproteins toward his long-term goal of designing synthetic metalloproteins of therapeutic value. Our studies reveal biochemical design principles that have advanced the field to the point where multi-cofactor metalloproteins like those involved in human cancer can be rationally designed and structurally characterized. Zinc finger proteins are the largest class of metalloproteins in the human genome and their gene regulation function is fundamental to numerous human cancers. ZFPs exhibit metal-induced protein folding events, where the ZFP is unfolded in the absence of zinc and folds into its biologically active form upon zinc ion binding. The coupled nature of metal-ion binding and protein folding obscured the thermodynamics of each since their discovery in the 1980’s. Using a simple designed peptide with the classic ZFP coordination motifs, the Gibney laboratory was able to decouple the thermodynamics and show that the cost of protein folding free energy (+0-5 kcal/mol) is minimal compared to the free energy of Zn(II) binding, -15 kcal/mol. Current work is focused on the interaction of zinc with human transcription factor IIB and the Wilms Tumor Suppressor.
Selected Publications:
Patents: None Grants over the last 5 years: No federal grant
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