System Development

** ****** ****** **** *********: 781-***-****

Lynn Mobile Phone: 617-***-****

MA 01905 Email ********.**@*****.***

High performing experimental biologist with 20 years of experience supporting drug discovery programs within the biopharmaceutical industry. Core expertise in developing cell-free and cell-based assays to support high throughput screening initiatives and detailed SAR support. Additional technical experience with laboratory automation and in vivo pharmacology including bioluminescence imaging.

Core Skills

In vitro Assay Development and High Throughput Screening:

• Expert in developing cell-free and cell-based assays to identify activators and inhibitors across multiple drug target classes including; protein and lipid kinases, G-protein coupled receptors and transport proteins.

• Proficient in multiple screening technologies;

o Cell-free platforms including; luminescence e.g. Kinase Glo, flourescence intensity e.g. ADP Hunter, fluorescence polarization trans-screener, Radioactive e.g.SPA.

o Cell-based platforms including: second messengers e.g.beta lactamase and luminescence, substrate accumulation by fluorescent intensity and mRNA levels by bDNA

• Supported early stage lead identification and late stage compound optimisation programs.

• Experience of supporting both small molecule and large molecule drug discovery programs.

• Expert in the evaluation and integration of high throughput screening platforms including; Zeiss and Robocon.

• Expert in laboratory automation and assay miniaturization.

• Experience in retrieving, analysing, storing and interpreting the large and complex data sets arising from high throughput screening campaigns consisting of millions of compounds.

In vivo Pharmacology:

• Expert in Bioluminescence imaging using the IVIS system.

• Developed and implemented bioluminescent mouse xenograft tumor models.

• Highly skilled in animal handling and administration of test substances through subcutaneous, IV, PO and hydrodynamic tail vein injections.

• Experienced in small animal surgery

Professional Experience

Novartis Institute For Biomedical Research (NIBR), Cambridge MA, 2011 to Present

Contract Scientist – Development and Molecular Pathways, Pathways Biology II

• Ran cell based High Content Imaging assay to support ongoing SAR, providing data for project team in a timely manner. Utilized HCI assay to see the effect of different classes of compounds on signal to determine MOA of lead compounds.

• Ran HCI assay and qPCR in primary cells to measure effects of oligonucleotides on knockdown of signal and of mRNA to determine MOA of lead compounds.

• Developed and automated HTRF assay to determine which cell line to be used in a HTS campaign.

Pfizer Inc., Research Technology Center, Cambridge, MA, 2001 - 2011.

Position held: Scientist – Nucleic Acid Therapeutics – Delivery Biology (2008 to 2011)

My primary responsibility is to develop efficient and safe delivery systems/formulations for nucleic acid based therapeutics. The most significant contributions that I have made to this mission include;

• Lead in vivo biologist for the oligonucleotide delivery biology group. Developed a novel Bioluminescent animal model designed to determine the effectiveness of our RNAi delivery systems/formulations.

• Contributed to the development of a novel in vivo bioluminescent xenograft model designed to address the accuracy of our in vitro assays and to predict the more likely outcomes in vivo.

• Developed an in vitro 384-well cell-based reporter gene assay system improving the throughput and efficiency of screening methods to prosecute thousands of delivery formulations..

• Identified novel uses of bDNA detection technology to address potential off-target effects of therapeutic oligonucleotides using a multiplexed assay that was able to rapidly monitor the effect on multiple genes.

Position held: Scientist – Kinase Center of Excellence – Target Biology (2004 to 2008)

Focussing on protein and lipid kinases the mission of our group was to establish new drug discovery programs in the areas of oncology and inflammation, and to develop novel platform technologies that could be adopted by the global Pfizer Research and Development community.

• Optimized Zeiss Ultra High Throughput Screening unit to run assays on six separate kinase targets simultaneously increasing throughput to thousands of IC50 determinations every two days.

• Developed a fluorescent polarization assay coupled to Evotec nanoliter dispensing technology for a specific high value kinase implicated in inflammation. This system retained high sensitivity and reproducibility of previous assays while decreasing the need for an expensive, limiting reagent.

• Investigated the impact of drug transport proteins on the translation between in vitro and in vivo pharmacocology for small molecule drug candidates. We developed two novel high throughput cell-based assays and transferred them to Zeiss Ultra High Throughput Screening system, where we screened a collection of 100,000 compounds. This data set allowed Pfizer to build a novel computational model that had an unprecedented level of accuracy with regards to predicting drug interactions with these transporters.

Position held: Scientist – Gene Family Initiative – Screening Technology (2001 to 2004)

Focussing on G-protein coupled receptors (GPCRs) the mission of our group was to delivery lead molecules to support early drug discovery programs in the area of cardiovascular and metabolic disease, disorders of the central nervous system and urogenital health. My most significant achievements include;

• Implementation of Pfizer’s first Zeiss Ultra High Throughput Screening system. Subsequently, I transferred this technology to Pfizer groups based in California and St Louis and acted as a technology super user and a consultant to the global Pfizer community with regards to assay development, time and cost efficiency and general trouble shooting.

• Assisted with the development of multiple cell-based assays designed to investigate GPCRs crossing aminergic, peptidergic and orphan receptor families. For a number of these assays I successfully transferred them to our high throughput assay platforms and screened Pfizer’s full file of over two million compounds.

• Contributed to multiple lead optimisation programs, providing biological assay support to drive SAR progression. Our efforts led to a number of our programs and lead molecules being adopted by the larger Therapeutic Area Teams, and were subsequently advanced to early clinical assessment.

Roche Products Ltd. Welwyn Garden City, England (1999-2001)

Position held: Research Scientist – Department of High Throughput Screening

My primary responsibility was to integrate the Zeiss Ultra High Throughput screening system into the work flow of the High Throughput Screening Department. A key part f this role required me to work closely with my colleagues to develop and transfer assays to the Zeiss system, after which I had primary responsibility to ensure assay robustness and quality was retained. Through my efforts, and the implementation of the Zeiss system, the number of data points generated by my department increased three-fold.

SmithKline Beecham, New Frontiers Science Park, England (1989-1999)

Position held: Senior Scientist – Department of High Throughput Screening

As a founding member of SmithKline Beecham’s UK screening group I was responsible for the design and implementation of the Robocon high throughput screening system. This novel equipment when coupled to commercial liquid handlers allowed us to run SmithKline Beecham’s first high throughput/low volume assays using 384-well assay plates. These advances significantly increased our screening capacity whilst simultaneously reducing operating costs, increasing assay quality and reducing run times. As the primary user for this system I was accountable for the daily maintenance of the Robocon, and for providing technical and scientific support to help support the needs of colleagues across multiple therapeutic teams.

Education

B.Sc. (Hons) - Applied Biological Sciences - University of the West of England Bristol (1989)

References

Available on request

Publications

Ye P, Kuhn C, Juan M, Sharma R, Connolly B, Alton G, Liu H, Stanton R, Kablaoui NM. Potent and Selective Thiophene Urea Templated Inhibitors of S6K. Bioorg Med Chem Lett. 2011 Jan 15;21(2):849-52. Epub 2010 Nov 21.

Stockman BJ, Kothe M, Kohls D, Weibley L, Connolly BJ, Sheils AL, Cao Q, Cheng AC, Yang L, Kamath AV, Ding YH, Charlton ME. Identification of allosteric PIF-pocket ligands for PDK1 using NMR-based fragment screening and 1H-15N TROSY experiments. Chem Biol Drug Des. 2009, 73(2):179-88.

Soulard P, McLaughlin M, Stevens J, Connolly B, Coli R, Wang L, Moore J, Kuo MS, LaMarr WA, Ozbal CC, Bhat BG. Development of a high-throughput screening assay for stearoyl-CoA desaturase using rat liver microsomes, deuterium labeled stearoyl-CoA and mass spectrometry. .Anal Chim Acta. 2008;627(1):105-11.

Jonathan R. S. Arch, Derek R. Buckle, Brendan J. Connolly, Andrew Faller, Ashley E. Fenwick, Kenneth J. Murray, Harshad K. Rami, Mark S. Smallridge, David G. Smith. Inhibition of Type 4 Cyclic Nucleotide Phosphodiesterase by 8-Chloroxanthines. Arch. Pharm. Pharm. Med. Chem. 1996, 329, 205-208.

Derek R Buckle, Jonathan R. S. Arch, Brendan J. Connolly, Ashley E. Fenwick, Keith A. Foster, Kenneth J. Murray, Simon A. Readshaw, Mark Smallridge, David G. Smith. Inhibition of Cyclic Nucleotide Phosphodiesterase by Derivatives Of 1,3-Bis (cyclopropylmethly) xanthine. Journal Of Medicinal Chemistry. 1994, 37, 476 - 485.

William J Coates, Brendan J. Connolly, Dashyant Dhansk, Sean T. Flynn, Angela Worby. Cyclic Nucleotide Phosphodiesterase Inhibition By Imidazopyridines: Analogues Of Sulmazole And Isomazole As Inhibitors Of The cGMP Specific Phosphodiesterse. Journal Of Medicinal Chemistry. 1993, 36, 1387 - 1392.

Brendan J. Connolly, P. Barnaby Willits, Brian H. Warrington, Kenneth J. Murray. 8-(4-Chlorophenyl)thio- Cyclic AMP Is A Potent Inhibitor Of The Cyclic GMP-Specific Phosphodiesterase (PDE Va). Biochemical Pharmacology. 1992, 44, 12, 2303-2306.

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