Engineering Hope in the Fight Against Brain Cancer

2011-01-08T04:44:00.000-08:00

Brain cancer is one of the most devastating diagnoses a person or family can receive. Bioengineering doctoral candidate Matt Dowling is using new methods to attack an illness for which there have been few other treatment options than surgery and radiation, and for which there is a high rate of reoccurrence. His proposal, "Gelatin Nanoparticles Containing Stabilized Vesicles: A Novel Chemotherapuetic Delivery System for Treatment of Malignant Glioma," earned him the 2005 Fischell Fellowship in Biomedical Engineering.

Trying to tackle a particular cancer provides Dowling with motivation and focus. The brain creates a very specific environmental challenge, and influences the design of his solution. If he is successful, however, others could build on and adapt his methods to other situations and treatments.

Dowling's research centers around vesicles, nanocontainers which form spontaneously in aqueous environments, encapsulating other molecules in their hollow centers. Our bodies use them to route nutrients, metabolites and chemical signals within and between cells. For this reason, scientists have been interested in their potential use as vehicles for targeted drug delivery—the ability to load the vesicles with the appropriate medication, and control where, when and how that medication is released.

Unfortunately, vesicles produced in the laboratory tend to be quickly targeted and "captured" by the macrophages in our immune system when injected into the bloodstream, greatly limiting their ability to reach their destinations. They are also unstable structures. Previous research has found the vesicles can be stabilized and spend more time in the bloodstream by coating their surface with a synthetic polymer known as polyethylene glycol (PEG). To combat glioma, however, Dowling is instead encasing the vesicles in gelatin nanoparticles, a natural polymer.

This is because gelatin nanoparticles have a rare advantage: they are one of the few that can traverse the blood-brain barrier, a tight seal which keeps toxins (including things perceived as toxins, like drugs) out of the brain, and only allows the passage of oxygen and nutrients. "The idea behind my proposal, says Dowling, "is to further explore the use of gelatin nanoparticles in treatment of brain cancer while adding a significant twist to the strategy: instead of just using the gelatin to carry the drug, it will also be a camouflage which allows a much more versatile drug container, the vesicle, to get into the brain tissue from the blood stream. This could result in an injectable form of therapy for malignant glioma, which would be immensely preferable over brain surgery."

Currently, Dowling is working with cell cultures, studying the conditions under which nanoparticle uptake occurs, and he is also experimenting with what he calls "mothership microcapsules" made out of another natural polymer, chitosan. Like their gelatin counterparts, the chitosan capsules protect the drug-carrying vesicles, but on a much larger scale: one "mothership" microcapsule may contain hundreds of vesicles. If ferromagnetic nanoparticles are added to the chitosan-vesicle mix during capsule formation, Dowling has found, they can then be guided to specific locations in the body with an electromagnetic field. He has also shown that the surface of his microcapsules can easily be joined with antibodies—immune system proteins whose mission is to target and evict specific threats, like viruses; or in this case, cancer cells. This combination may further increase the tumor-targeting capabilities of his drug delivery system. Future work will include translating this system down to the nanoscale and testing its ability to cross the blood-brain barrier.

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Matthew Dowling Profile

2011-01-08T04:41:00.000-08:00

Professional Profile

Over 20 years of leadership experience as a technical and management consultant across a wide range of industries, including telecommunications, financial services, enterprise software, e-business, and Internet services. This includes extensive background in systems integration, project management, software development, vendor management, and implementing software engineering processes. Strong senior management, organizational leadership and communication skills complement systems experience.

Professional Summary

Corporate Leadership:

Successfully led organizations ranging from small start-up with total operations responsibility, to large enterprise IT groups with over 500 technical professionals
As CTO of Pacific Bell Communications, successfully delivered over 50 systems to internal customers
Achieved significant improvements in operational efficiency through comprehensive software process re-engineering program: increased project commitments met, reduced time-to-market, raised software development productivity, and lowered new trouble reports rate

Information Systems Development:

Managed teams of technical professionals to develop and deploy business systems in complex computing environments, with a high degree of customer satisfaction
Saved Pacific Bell over $10 million per year by developing and implementing a synchronization process that identified and corrected monthly billing errors in 9 internal systems
Oversaw extensive system enhancements and maintenance efforts for numerous information systems environments

Project Management:

Managed individual projects and large project portfolios
Successfully turned around several failing multi-million dollar projects, resolving structural problems and delivering desired outcomes to customers
Effectively managed large cross-functional teams, in a matrixed environment, to develop and implement web-based business solutions

Vendor Management:

Managed major software development and contract negotiations with a wide range of vendors
Worked with major hardware and software vendors to purchase, integrate, and install local, regional and international information systems
Partnered with major vendors (Accenture, Deloitte Consulting, PWC, etc.) to deliver numerous high-value projects
Managed major software development and contract negotiations with a wide range of vendors

Business Process Management:

Established and implemented development strategies for integrated systems and platforms
Developed, implemented, and managed enterprise-wide process management and improvement methodology
Developed, implemented, and managed enterprise Key Performance Indicators system
Established and implemented development strategies for integrated systems and platforms

Professional Experience

Syncsort Inc.

SVP, Worldwide Alliances

Woodcliff Lake, NJ

2008 - 2010 (May)

Responsible for developing the worldwide Partner strategy for Syncsort, starting from a base of three partners. Today Syncsort has over 40 partners including companies such as; IBM, Microsoft, Teradata, Netezza, NetApp, Vertica, Trillium, Sybase and EMC - to name a few.
Responsible for developing an OEM program for Syncsort. Major deals include the closing of multi-million dollar OEM deals with BMC and IBM. Today's pipeline exceeds $20M with companies like NetApp, Microsoft and EMC.
Responsible for the development of the company's Business Intelligence (BI) strategy. Also, involved with the creation of Market plays such as ClickStream Processing, Database Marketing and Legacy Migration.

Director, Cisco Strategic Alliance

Palo Alto, CA

2008 - 2008

Leading the effort to analyze the potential strengths and weaknesses of the HP - Cisco relationship.
Responsible for communicating the value of the Cisco products and services to the HP sales force in order to increase the number of sales opportunities.
Responsible for addressing senior management's commitment, finding the calibre of resources devoted to the alliance, linking of budgets and resources with strategic priorities, measuring and rewarding alliance performance, and assessing the performance and results of the alliance.

Informatica

Senior Director, Global Alliances
Redwood City, CA
2005 - 2008

Proactively engaging with premier and strategic partners to identify new sales opportunities and help influence existing opportunities - partners that include HP, SUN, IBM, EMC, Informatica, Ascential, SPSS, MicroStrategy and Logicalis
Identifying and engaging with regional Systems Integrators whom will deliver new leads globally and specific accounts - SIs that include Accenture, BearingPoint and PWC
Created incremental 10% growth in sales revenue year over year - currently a $40M per year Division

Sybase

Director, Communications Industry
Dublin, CA
2002 - 2005

Rolled out an integrated vertical e-business solution for telecommunications, from concept to product release
Negotiated integration and channel relationships with hardware and software vendors, and top-tier system integrators
Responsible for creating and executing a Telecommunications vertical strategy leveraging existing Sybase assets

Montclare Technologies
CIO & Vice President, Professional Services
Oakland, CA
1999 - 2002

Managed a successful 65-person Internet professional services organization
Responsibilities included business development, sales, business consulting, project management, creative design, application development, and application integration
Provided executive-level strategic consulting to over 75 clients in the areas of Internet technology, hosting, network infrastructure, and e-business solutions
Part of small team that spun off a supply chain solutions company that became Sitoa Corporation

Cygent

Director, Product Strategy
San Francisco, CA
1999 - 1999

Developed business (MRD) and functional (PRD) requirements for first e-Commerce application for the Telecommunications industry
Evaluated the competitive landscape and made recommendations regarding product pricing and positioning, strategic partnerships, and customer profiles
Provided sales engineering support and consulting to prospective clients on product implementation and related infrastructure requirements

Charles Schwab

Director, Intranet
San Francisco, CA
1997 - 1999

Provided managerial and project management oversight for a wide range of Intranet technology initiatives across the corporation
Created a virtual paperless internal environment using the Intranet, saving the company over $3 million per year in data processing and publishing costs
Introduced Webcast technology, saving the company $1 million per year in travel costs

Pacific Bell Communications

Chief Systems Architect (CTO)
Pleasanton, CA
1983 - 1997

Oversaw various facets of the PBC's system architecture reporting to the CIO
Managed a $500 million budget over a three-year period
Responsible for developing and managing business development strategy and alliances
Performed multiple roles during rapid career progression, from initial position as programmer

Education

California State University, Hayward
Bachelor of Science in Mathematics with an option in Computer Science, Graduated with Honors

Recognition

Qualified for Informatica 2006 President's Club by obtaining 130% of quota
Nominated for the Charles Schwab "1998 IT Manager of the Year Award"
Five time recipient of the Charles Schwab "Excellence In Service Award"
Recipient of the "1990 Pacific Bell Chairman Quality Award"