Powering the New Engineer https://www.eng.ufl.edu/newengineer News from Herbert Wertheim College of Engineering at the University of Florida Mon, 23 Dec 2019 21:57:27 +0000 en-US hourly 1 https://wordpress.org/?v=5.3.2 A Look Back at Top Stories from 2019 https://www.eng.ufl.edu/newengineer/news/a-look-back-at-top-stories-from-2019/ Mon, 23 Dec 2019 21:28:05 +0000 https://www.eng.ufl.edu/newengineer/?p=28007
Young faculty win top honors

UF engineering faculty received prestigious awards this year. Domenic Forte (ECE), Maitane Olabarrieta (ESSIE) and Aysegul Gunduz (BME) garnered Presidential Early Career Awards for Scientists and Engineers (PECASE) that include a trip to the White House. Three young investigators won awards for innovating security – Ryan Houim (MAE), Kyle Hartig (MSE), and Yier Jin (ECE). Six researchers received NSF Early Career Awards – Antarpreet Jutla (ESSIE), Kyla McMullen (CISE), Alexander Grenning (ChemE), Blanka Sharma (BME), Denise Simmons (ESSIE) and David Hibbitts (ChemE).

  • UF ENGINEER RECEIVES ECASE-ARMY AWARD and  pecase

  • Olabarrieta Receives the pecase award

  • Gunduz receives Presidential Early Career Award for Scientists and Engineers

  • New UF Engineering Faculty Win Young Investigator Awards For Innovating U.S. Security

  • UF Engineer Uses 3D Audio Rendering and Perception to Aid Firefighters

  • UF Biomedical Engineer Pursues Understanding of Natural Killer Cells

  • Hibbitts Receives Prestigious NSF CAREER Award

In the spotlight this year

Engineering alumni gained acknowledgement and acclaim in 2019, including Linda Parker Hudston (ISE), who was elected to the National Academy of Engineers and NVIDIA founder Chris Malachowsky (ECE) who was inducted into the Florida Inventors Hall of Fame.

  • UF Alumna Linda Parker Hudson Elected to National Academy of Engineering

  • NVIDIA Founder Chris Malachowsky Inducted Into Florida Inventors Hall Of Fame

Engineering for better healthcare

From biomedical engineering to mechanical engineering, UF faculty completed ground-breaking research in the healthcare field this year.

  • BIOMEDICAL ENGINEERS AT UF HAVE OSTEOARTHRITIS PAIN ON THE RUN

  • UF Research Team Aims to Reduce Cost of Drug Development Using 3D-Printed Living Tissues

  • UF Engineer makes  Breakthrough in insulin regulation pathway

Safer, Smarter, Better – Innovations that transform the future

The use of AI is leading to innovations for safer roadways and intersections; coastal and environmental engineers are leading the way in creating resilient coastal communities.

  • UF Engineer Leads Collaboration for Safer Roadways

  • iCoast- A Multidisciplinary Approach to Creating Resilient Coastal Communities

Engineering College Growth

The Herbert Wertheim College of Engineering added a new department in 2019 to study and enhance engineering education.

  • UF Adds Fully Dedicated Engineering Education Department to Engineering College

Students shine in design competitions

Teamwork among students and with experienced faculty brought many wins to UF this year, most notably the 2019 Engineering Deans’ Cup.

  • University of Florida wins 2019 Engineering Deans’ Cup

  • UF-SIT Team Takes First in Pwny Race at NYU’s CSAW Competition

  • Team GatorWings Takes First Place in DARPA SC2

To see more stories from 2019 about faculty, students and alumni, visit the Herbert Wertheim College of Engineering web site news page “Powering the New Engineer”. https://www.eng.ufl.edu/newengineer/

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Thomas Lutza Awarded UF Outstanding Four-Year Scholar https://www.eng.ufl.edu/newengineer/essie/thomas-lutza-awarded-uf-outstanding-four-year-scholar/ Mon, 23 Dec 2019 15:53:10 +0000 https://www.eng.ufl.edu/newengineer/?p=28077

Curtis Taylor, Ph.D and President Fuchs with Thomas Lutza holding award

Curtis Taylor, Ph.D, Thomas Lutza (BSCE ’19) and President Fuchs, Ph.D. at the Outstanding Leaders & Scholars ceremony

Thomas Lutza (BSCE ’19) was named a University of Florida (UF) Outstanding Four-Year Scholar at the Outstanding Leaders & Scholars ceremony on December 13. Lutza just received a bachelor’s degree in civil engineering from the Herbert Wertheim College of Engineering.

Every commencement, UF and the Alumni Association select outstanding students based on overall achievements. The committee takes into account grade point average as well as academic awards, presentations and research projects.

“This award means everything to me, I believe is it is a representation of hard work and perseverance,” Lutza said. “I have been able to work with multiple research groups, design teams, and student organizations that have truly provided a well-rounded educational experience.”

Through resilience and determination, Lutza maintained a 4.0 GPA while participating in structures and materials research groups and leading UF’s American Society of Civil Engineers (ASCE) concrete canoe team. He served as concrete canoe head captain in 2018 and then as ASCE conference chair.

Lutza credits Dr. Robert Thieke, Department Head of the Department of Civil and Coastal Engineering and academic advisor, as the most influential individual in his collegiate career. Lutza says Dr. Thieke served as a professor, academic advisor, concrete canoe team advisor and role model.

“Thomas is an absolutely dedicated and industrious individual who has displayed outstanding teamwork skills in roles both as a member and a leader. At the same time, he has achieved academically at the highest level at UF and continues to do so.  He compliments this outstanding academic ability with a very good practical sense and is as much at home tackling hands-on design projects as he is doing theoretical engineering computations.,” Dr. Thieke said.

After receiving his bachelor’s, Lutza will continue pursue a master’s degree in structural engineering in the College within the Engineering School of Sustainable Infrastructure & Environment (ESSIE).

“Because of the University of Florida, more specifically ESSIE, and the amazing people I’ve gotten to know along the way, I am now more confident than ever to move confidently in a direction that I never could have imagined,” said Lutza.


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Hibbitts Receives Prestigious NSF CAREER Award https://www.che.ufl.edu/blog/hibbitts-receives-prestigious-nsf-career-award/ Thu, 19 Dec 2019 13:31:59 +0000 https://www.eng.ufl.edu/newengineer/?p=28001 Aim for Reform, Not Just Relief https://www.eng.ufl.edu/newengineer/essie/aim-for-reform-not-just-relief/ Wed, 11 Dec 2019 13:40:00 +0000 https://www.eng.ufl.edu/newengineer/?p=27979
RETHINKING HOW TO REBUILD AFTER HURRICANES

This article is written by David O. Prevatt, Jason von Meding and Ksenia Chmutina and was originally published in The Conversation.

The neighborhood known as The Mudd suffered disproportionate damage, a reflection of the Bahamas’ history. AP Photo/Fernando Llano

The neighborhood known as The Mudd suffered disproportionate damage, a reflection of the Bahamas’ history. AP Photo/Fernando Llano

Risk rooted in colonial era weighs on Bahamas’ efforts to rebuild after Hurricane Dorian

When Hurricane Dorian made landfall on Great Abaco Island in the Bahamas on Sept. 1, 2019, it packed winds of up to 185 miles per hour and a 20-foot storm surge. A day later, it ravaged Grand Bahama for 24 hours.

Across both islands, the storm brought “generational devastation.” Thousands of houses were leveled, telecommunications towers were torn down, and roads and wells were badly damaged. The cost to the Bahamas has been estimated to be up to US$7 billion – more than half of the country’s annual economic output.

But not all structures and communities in Dorian’s path were equally affected. The Structural Extreme Events Reconnaissance Network, or StEER – a research group we participate in – found that while structural failure was widespread, houses intentionally built to resist high wind and storm surge fared much better.

The problem is that not everyone has access to a house that can weather a storm like Dorian. The different ways in which Abaco and Grand Bahama – and their residents – were affected by the same event is yet another example of how disaster impacts are rooted in the historical development of society.

This happens around the world time and again. To really understand what happened in the Bahamas – and determine how it should rebuild – one needs to look back at how society has developed there.

Dominant (and safe) narratives

Certain narratives tend to dominate the media in the aftermath of disasters: death and destruction, heroes that come to the rescue and “villains” that allegedly capitalize on misery or are to blame for the calamity. In recent years, what could be called a climate breakdown narrative that links disasters to climate change has also become prominent.

But we can sometimes learn even more by examining the narratives that are not present.

The historical context of injustice, discrimination and inequality – experienced through social structures that cause harm to certain people – is often missing. This context informs today’s risk.

In the Bahamas, we see this kind of accumulated risk most clearly among the Haitian diaspora and Haitian Bahamians, who are stigmatized and face many barriers to full participation in society.

Engineers from the Structural Extreme Events through Reconnaissance research group inspected buildings damaged after the hurricane to capture how failures happened. Justin Marshall

Engineers from the Structural Extreme Events through Reconnaissance research group inspected buildings damaged after the hurricane to capture how failures happened. Justin Marshall

The most catastrophic damage from Dorian occurred in communities like “The Mudd” – a shantytown housing the nation’s largest Haitian immigrant community – where land is not owned by residents, and daily survival is paramount. People there trade the risk presented by massive hurricanes for the necessity of a place to live.

This trade-off can only be understood as part of the story of risk creation.

Natural hazards are not disasters

Disasters are not “natural events”; they are long-term processes of accumulated risk and impact.

Yes, nature shows its unyielding force through earthquakes and tsunamis. But in their differential impacts, disasters can actually be seen as social and political manifestations of injustice. In the Bahamas, inequality, poverty, political ideology, class and power relations lead to the buildup of unequal risks that make some people considerably more vulnerable than others.

For every inadequate building, there is a social context.

The same phenomenon plays out across the Caribbean – in Puerto Rico, Haiti, Dominica – and around the world as a protracted class divide.

Of course, people know that Caribbean housing is often ill-prepared for hurricanes. This is linked to inappropriate long-standing structural design choices and the limited enforcement of building codes. Both of these problems have supposedly been solved on paper, but the best technical solutions very often fail to grapple with social and political realities – and the root causes of disasters.

 Two houses side by side - only one survived the storm surge. Daniel Smith, Structural extreme Events Reconnaissance Network, Author provided

Two houses side by side – only one survived the storm surge. Daniel Smith, Structural extreme Events Reconnaissance Network, Author provided

What turned Hurricane Dorian into an epic disaster, particularly in places like The Mudd, was the lack of access to the resources necessary to achieve wellness everyday and safety during the storm.

Accumulated risk in the Bahamas

When Europeans arrived in 1492, they committed atrocities against the indigenous peoples that lived there. The Caribbean was rapidly turned into a site to sustain and protect colonial circulations of goods, money and slaves. Between the 16th and 19th centuries, an estimated 5 million Africans were enslaved and transported to the Caribbean. Half ended up in British territorial possessions, such as the Bahamas.

Colonization created the conditions for the chronic levels of risk that we see today among the descendants of enslaved people.

While slavery was abolished in these territories in the 1830s, most descendants of slaves remained indebted and were forced to undertake low-wage agricultural labor for mostly white absentee landowners. Inequalities, injustices and discrimination were thus institutionalized in the colonies, and remain largely in place within now-independent societies.

Alongside invasion, conquest and colonization, contemporary vulnerabilities in the Bahamas reflect laissez-faire historical attitudes toward addressing long-term risk. This is the foundation of contemporary structures of governance, society and the economy – and a big part of why today poor Bahamians, Haitians and Haitian Bahamians struggle for survival.

 Engraving depicting Christopher Columbus landing on Hispaniola. His expedition originally landed in the Bahamas and was met by the Lucayans, who were wiped out along with an estimated 12-15 million indigenous people across the Caribbean. Theodor de Bry/Library of Congress

Engraving depicting Christopher Columbus landing on Hispaniola. His expedition originally landed in the Bahamas and was met by the Lucayans, who were wiped out along with an estimated 12-15 million indigenous people across the Caribbean. Theodor de Bry/Library of Congress

How can we do better?

Moving into the recovery phase of Dorian is daunting. Affected communities need support to not just return to “normal” but address structural injustice. The probability of stronger storms under climate change – and impacts distributed primarily onto the most marginalized – continues to increase.

A historically and socially conscious approach to recovery and reconstruction could address not only shelter and infrastructure needs, but broader issues of equity and justice.

Understanding the origins of risk can inform better decisions about building back (or not). Ironically, the most vulnerable often continue to be left with no choice but to live in the most exposed areas.

Optimum building codes, planning policies and design strategies are critical. Much of the detailed hurricane-resistant structural knowledge is proven and available – small design changes make a substantial difference.

But without a plan for achieving equity and establishing basic rights and access for all, solutions will serve mostly the privileged. Colonial patterns of displacement, dependency and disadvantage are likely to be reinforced.

Dorian, like so many others recently, was a monster storm. But blaming disasters on nature – or human-induced climate change – allows those with power to maintain the status quo and to avoid their responsibility for the failures of development.


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For UF Engineering Alumnus and Wife, a Big Part of Living is Giving https://www.eng.ufl.edu/newengineer/alumni-spotlight/for-uf-engineering-alumnus-and-wife-a-big-part-of-living-is-giving/ Mon, 25 Nov 2019 18:03:07 +0000 https://www.eng.ufl.edu/newengineer/?p=27907

Volunteers behind a table of donated items at Air Unlimited warehouse.

Volunteers sort and prepare items to be shipped to the Abacos

Charles “Chick” (BSCE ’72) and Lisa Gregg, UF Alumni Association life members, were vacationing in Colorado with their friend and partner, Mark Neubauer, when news of Hurricane Dorian’s imminent landfall reached them. Very quickly, their carefree vacation turned into a tense long weekend glued to the Weather Channel, waiting to learn the fate of the Abaco Islands and their inhabitants. The catastrophe affected Chick, Lisa and Mark directly, as they are the owners of Air Unlimited, a luxury airline service in Sanford, Florida, that offers scheduled flights to Marsh Harbor and Treasure Cay on Great Abaco as well as charter flights throughout the Bahamas and the southeastern United States. Chick and Mark started the airline after both had retired, turning their love of flying into a thriving regional business.

When Category 5 Hurricane Dorian arrived at the islands on September 1 and remained almost stationary over the area until September 3, the 185-mph winds, torrential rain, and storm surges devastated the Abacos and other areas of the Bahamas, leaving nearly 70,000 people homeless, most without food, water or shelter. As the dreaded news of a major impact caused by Dorian started pouring in, the Greggs and Neubauer began making plans on how to help the devastated island, a skill for which engineers are well trained. Using WhatsApp, they began contacting friends and members of their business community. Overnight, their luxury planes turned into cargo carriers. Their airport hangar and warehouse filled with donations from local people. Within a day and a half of the storm’s passing, Neubauer traveled to the Abacos via helicopter to assess the situation. The partners quickly realized that, while relief efforts were critical, rescue operations would also play an important role in their efforts.

The first Air Unlimited planes ferried relief supplies to those staying in the islands but also evacuated people who needed medical attention from the islands to Florida. Florida House Representative Scott Plakon set up an office at the Sanford, FL, hangar, teaming up with Air Unlimited and other members of the Abaco Flight Support group to help organize relief services, supply drops, and to help with the logistics of getting stranded Floridians back home.

After initial flights into Nassau on Grand Bahama, Air Unlimited and other volunteer pilots switched their delivery site to Sandy Point the moment it was cleared, as it was the only functioning airstrip on Abaco after the storm. From there, they used boats to get supplies to the smaller surrounding islands, where inhabitants had beencut off from all outside assistance for almost a week.

House demolished by hurricane.

Homes destroyed by Category 5 Hurricane Dorian

On September 6, the Greggs and Neubauer, along with Abaco Flight Support, set up another distribution center at Spanish Wells on the nearby island of Eleuthera, where many more boats were available. When Hurricane Andrew hit Eleuthera in 1992, the Abaconians were of great help to the people of Spanish Wells, and they were happy to return the favor now. The fishermen from Spanish Wells helped distribute supplies and opened their homes to Abaconian refugees to assist them in recovering from the storm. Some of the refugees are already able to sustain themselves and return to their islands. As of November 1, there are 60 Abaconian children enrolled in Spanish Wells schools.

“Dorian struck the Abacos from September 1 – September 3, and we flew our first planeload of supplies to an airstrip in Nassau on September 5. Within five days, our supply chain had become so efficient that by September 10, when we sent two A320 Airbuses to North Eleuthera loaded with 30,000 pounds of supplies, everything was distributed via the boats by the next day,” Chick said. “When the boats were going to the out islands, it was very challenging to offload the supplies because all docks and piers were gone,” added Lisa.

As time went on, the Air Unlimited team began to receive specific requests from people in the Abacos, which they sent out to their community via social media. “We would receive the needed items by the end of the day,” said Melissa Manchester, the office manager at Air Unlimited. “Everyone was extremely responsive.” Air Unlimited also set up a GoFundMe® page, where they accepted donations to purchase fuel for their relief planes and for those of other pilots who donated their planes and their time to help in the relief efforts.

By September 20, as the need for essential relief supplies decreased, Air Unlimited shifted their efforts to include flying professionals – medical personnel, engineers, builders, etc. – to Marsh Harbor and Treasure Cay on charter flights to help begin rebuilding efforts.*

“We will continue to collect requests and provide needed supplies to the people of the Abaco Islands,” Mark said. “One of our biggest challenges in the beginning was finding people and finding out what they needed to survive. Since we had been flying to the Abacos on a regular basis, we were well situated to understand the challenges survivors faced and be successful in helping out. Today we have a sound system set up that will sustain our efforts.”

Warehouse full of donated supplies

Within five days of the hurricane’s landfall, 30,000 pounds of supplies were flown to the Abacos for distribution

In addition to transporting supplies, Air Unlimited flights are now offered to homeowners hoping to rebuild, as well as numerous volunteers doing everything from helping with the cleanup initiative to rescuing homeless pets.

Sustaining tourism in the remainder of the Bahamas will ultimately be vital to aid in the rebuilding of devastated areas. Air Unlimited has recently established scheduled flights to North Eleuthera to provide a continued destination point for visitors to the Caribbean.

As the Abacos begin to heal from Hurricane Dorian, Chick, Lisa and Mark are re-establishing their business in the Bahamas, serving people traveling there and continuing to give support to the citizens of the islands. “When giving of yourself or your treasure, you usually get more in return than you put in,” Chick noted.

For these UF alumni and friends, an important part of living is indeed giving.

*To view early stages of the relief efforts – donations, volunteers and hangar activities – visit Air Unlimited’s Facebook page.


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ESSIE New Faculty Hires https://www.eng.ufl.edu/newengineer/essie/essie-new-faculty-hires/ Thu, 21 Nov 2019 18:51:47 +0000 https://www.eng.ufl.edu/newengineer/?p=27927

The Engineering School of Sustainable Infrastructure & Environment (ESSIE) is excited to welcome seven new faculty members.

Katherine Deliz Quiñones, Ph.D.

Katherine Deliz Quiñones

Lecturer
Department of Environmental Engineering Sciences

Research Areas: Microbiome Engineering, Remediation, Ecotoxicology, Ecosystem and Social Resilience

B.S., Biology, 2000, University of Puerto Rico
M.S., Biology/Limnology, 2004, University of Puerto Rico, Mayagüez
Ph.D., Environmental Engineering Sciences, 2013, University of Florida

Christopher Ferraro

Assistant Professor
Department of Civil & Coastal Engineering

Research Areas: Infrastructural Materials, Cement and Concrete Testing and Mass Concrete

B.S., Civil Engineering, with honors, 1998, University of Florida
M.S., 2003, University of Florida
Ph.D., 2009, University of Florida

Christopher Ferraro, Ph.D.

Rui Guo, Ph.D.

Rui Guo

Lecturer
Department of Civil & Coastal Engineering

Research Areas: Multimodal Traffic Safety, Sustainable Transportation and Air Transportation

B.S., 2008, Southeast University
Ph.D., 2015, University of South Florida

Antarpreet Jutla

Associate Professor
Department of Environmental Engineering Sciences

Research Areas: Water and Health, Flood Forecasting, Satellite Remote Sensing Applications in Hydrology, Climate Change

B. Tech. 2001. Agricultural Engineering, Punjab Agricultural University, India.
M.Tech. 2003. Water Resources, Soil and Water Engineering Punjab Agricultural University, India.
M.Sc. 2006. Water Resources, Civil and Geological Engineering, University of Saskatchewan, Canada.
Ph.D. 2011. Water Resources,Civil and Environmental Engineering, Tufts University, USA.

Antarpreet Jutla, Ph.D.

Brian Phillips, Ph.D.

Brian Phillips

Associate Professor
Department of Civil & Coastal Engineering

Research Areas: Structural Dynamics, Structural Control, Wind Engineering, Earthquake Engineering, Cyber-Physical Systems

B.S., University of Pittsburgh
M.S., University of Illinois
Ph.D., University of Illinois

Katherine Todd-Brown

Assistant Professor
Department of Department of Civil & Coastal Engineering

Research Areas: Soil Carbon Dynamics, Earth System Models, Pore-to-Global Scaling, ModelData Integration, Simulation Analysis

B.S., Mathematics, 2004, Harvey Mudd College
Ph.D., Earth System Science, 2013, University of California Irvine

Katherine Todd-Brown, Ph.D.

Xilei Zhao, Ph.D.

Xilei Zhao

Assistant Professor
Department of Department of Civil & Coastal Engineering

Research Areas: Dynamic Traffic Network Modeling, Civil Infrastructure Systems, Future Mobility Systems Planning

B.E., Civil Engineering, 2013, Southeast University
MSE, Applied Maths and Statistics, 2017, Johns Hopkins University
Ph.D., Civil Engineering, 2017, Johns Hopkins University

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ESSIE Letter from the Director Fall 2019 https://www.eng.ufl.edu/newengineer/essie/essie-letter-from-the-director-fall-2019/ Thu, 21 Nov 2019 18:51:25 +0000 https://www.eng.ufl.edu/newengineer/?p=27951

Greetings from Gainesville,

Faculty in the Engineering School of Sustainable Infrastructure & Environment (ESSIE) are leading a new long-term program focused on monitoring, understanding and managing threats along the Florida coastline. This iCoast initiative is a multidisciplinary effort including many colleagues from the Herbert Wertheim College of Engineering and the University of Florida.

Please join us in welcoming five new faculty in the Department of Civil & Coastal Engineering and two new faculty in the Department of Environmental Engineering Sciences. These new hires complement and expand the diverse research and teaching skills within our faculty and enhance opportunities for collaboration within and beyond ESSIE.

Our students continue to shine in and out of the classroom. The ASCE concrete canoe and student steel bridge teams continued their long history of success in national competitions, placing first and second overall, respectively.

We look forward to a bright future educating the next generation of change makers and leading research that supports a sustainable and thriving Florida.

Kirk Hatfield Signature
Dr. Kirk Hatfield
Director,
Engineering School of Sustainable Infrastructure & Environment

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UF Engineer Examines CRISPR Technology in CANCER Therapy https://www.eng.ufl.edu/newengineer/carousel/uf-engineer-examines-crispr-technology-in-cancer-therapy/ Wed, 20 Nov 2019 20:36:47 +0000 https://www.eng.ufl.edu/newengineer/?p=27889
Gene being edited and Piyush Jain, Ph.D.This article was originally published in The Conversation.
How gene-edited white blood cells are helping fight cancer

For the first time in the United States, a gene editing tool has been used to treat advanced cancer in three patients and showed promising early results in a pilot phase 1 clinical trial. So far the treatment appears safe, and more results are expected soon.

To develop a safer and more effective treatment for cancer patients, scientists from the University of Pennsylvania, the Parker Institute for Cancer Immunotherapy in San Francisco and Tmunity Therapeutics, a biotech company in Philadelphia, developed an advanced version of immunotherapy. In this treatment, a patient’s own immune cells are removed from the body, trained to recognize specific cancer cells and then finally injected back into the patient where they multiply and destroy them.

Unlike chemotherapy or radiation therapy, which directly kills cancer cells, immunotherapy activates the body’s own immune system to do the work. This team used a gene editing tool called CRISPR to alter immune cells, turning them into trained soldiers to locate and kill cancer cells. By using this technique, the team hoped to develop a more effective form of immunotherapy with minimal side effects.

I am trained as a pharmaceutical scientist and a biomolecular engineer, and I was particularly interested to learn about this new therapy because my lab focuses on editing the gene editors. In particular, I am trying to develop even better CRISPR-based gene editors for the diagnosis and treatment of cancer and other disorders. We combine chemistry, biology and nanotechnology to engineer, control and deliver gene editing tools more efficiently and precisely.

A pseudo-colored scanning electron micrograph shows two T-cells (red) attacking a cancer cell (white). Researchers are creating more powerful cancer treatments by editing the genes inside the T-cells.

A pseudo-colored scanning electron micrograph shows two T-cells (red) attacking a cancer cell (white). Researchers are creating more powerful cancer treatments by editing the genes inside the T-cells. Rita Elena Serda, Duncan Comprehensive Cancer Center at Baylor College of Medicine, National Cancer Institute, National Institutes of Health, CC BY-NC

Training the immune cells to find and kill cancer

The first step in making these tumor-killing cells used in the cancer drug trial was to isolate the T-cells – a type of white blood cells that fights pathogens and cancer cells – from the blood of the cancer patients. Two patients with advanced multiple myeloma and one patient with myxoid/round cell liposarcoma were enrolled for this study.

To arm the T-cells and bolster their tumor-fighting skills without harming normal cells, scientists genetically engineered the T-cells – disabling three genes and adding one gene – before returning them to the patients.

The first two of these deleted genes encode T-cell receptors, which are proteins found on the surface of the T-cells that can recognize and bind specific molecules, known as antigens, on cancer cells. When these engineered T-cells bind to these antigens, it allows them to attack and directly kill the cancer cells. But the problem is that a single T-cell can recognize multiple different antigens in the body, making them less focused on finding the cancer cells. By eliminating these two genes, the T-cells are less likely to attack the wrong target or the host, a phenomenon called autoimmunity,

In addition, they disrupted a third gene, called programmed cell death protein 1, which slows down the immune response. Disabling the programmed cell death protein 1 gene improves the efficiency of T-cells.

The final step in the transformation of these cells was adding a gene which produces a new T-cell receptor that recognizes and grabs onto a specific marker on the cancer cells called NY-ESO-1. With three genes deleted and one added, the T-cells are now ready to fight cancer.

Where is CRISPR in this clinical trial?

So how exactly did this team edit a T-cell? They utilized CRISPR/Cas9 gene editing technology that uses two components: a guide CRISPR molecule that finds and binds the target gene site; and a molecular scissor, Cas9, that snips the DNA, ultimately disabling the gene.

The team used electroporation, a technology that creates temporary holes in the cell membrane, to deliver the Cas9 protein along with the guide molecules that targeted the three genes of interest in millions of T-cells.

After disrupting the three genes with CRISPR, the team used a safe, deactivated virus to deliver a gene to the T-cell that would enable it to recognize the cancer-specific marker – NY-ESO-1. Removing these genes from millions of cells and then allowing the T-cells to multiply into billions of cells outside the body in petri dishes can take several days to weeks.

Four days before injecting the CRISPR-modified T-cells, the team gave each of the three patients several doses of chemotherapy drugs to deplete the existing white blood cells in their bodies.

Finally, approximately 100 million modified T-cells per kilogram of body weight were injected into the patients as a single infusion.

 After modifying the T-cells by clipping out three genes with CRISPR and adding a new one, the immune cell becomes better at locating and killing cancer cells. Piyush Jain, CC BY-SA

After modifying the T-cells by clipping out three genes with CRISPR and adding a new one, the immune cell becomes better at locating and killing cancer cells. Piyush Jain, CC BY-SA

Promising future of CRISPR

The team monitored the patients continuously for the first 28 days after injecting the T-cells. Then they followed up monthly for six months; after that every three months by monitoring any adverse events such as immune reaction. The T-cell therapy is frequently associated with various side effects such as fever, muscle pain, headaches, confusion, seizures, low blood pressure, bleeding disorders and multiple organ dysfunction. The team noted no signs of toxicity in any patient, which is exciting.

But the first patient with advanced multiple myeloma had continued growth of a tumor after 60 days. While the treatment seemed not so successful for the first patient, the phase 1 clinical trial is mainly designed to test the safety, and the team reported no toxicity to any patient.

The second patient with advanced myxoid/round cell liposarcoma was monitored using serial CT scans and seemed stable after 90 days. The third patient with multiple myeloma started the trial recently and is too early for any results. The fact that there were no serious toxicity issues with this new therapy involving the CRISPR-based gene editing technology in cancer patients is a remarkable step toward the broad use in the clinic.


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Engineering Research Deepens Understanding of Glucose-Insulin Interaction https://www.eng.ufl.edu/newengineer/bme/engineering-research-deepens-understanding-of-glucose-insulin-interaction/ Fri, 15 Nov 2019 17:06:38 +0000 https://www.eng.ufl.edu/newengineer/?p=27869
UF biomedical engineer discovers alternate mode of GABA release from pancreatic beta cells

When insulin is secreted from beta cells in the pancreas to control glucose levels in the blood stream, GABA is also released from the cells to calm them so that the cells can prepare for the next pulse of insulin secretion. Having a stable insulin level is key to the functioning of a healthy pancreas. Impairment to beta cell GABA biosynthesis or release of GABA from the cell could leave islet tissue vulnerable to dysfunction or inflammation associated with type 1 and type 2 diabetes.

Edward Phelps, Ph.D., an assistant professor in the J. Crayton Pruitt Family Department of Biomedical Engineering at UF, Walker Hagan, Ph.D. student in the Phelps Lab, and an interdisciplinary research team* have developed a method to measure where and how gamma amino-butyric acid (GABA) is released from beta cells in the pancreas. Dr. Phelps and his colleagues have published a paper on their findings in Nature Metabolism, 2019 Nov 15; 11(1).

GABA appears in beta cells from the pancreas at nearly the same concentrations as in nerve cells of the brain. For the last 30 years, scientists thought that GABA was released from the beta cells in the same manner as in the nerve cells. In the brain, GABA is stored in small sacs (vesicles) at the end of the nerve cell. When a nerve impulse stimulates the vesicles in the axon of the cell to transmit the impulse to the next nerve cell, GABA is also secreted from the vesicles. GABA acts to calm the nerve so that it is ready for the next impulse. However, scientists were unable to locate a vesicular GABA transporter in 99% of beta cells, thus limiting the traditional explanation for GABA release from beta cells in the pancreas.

During his early research in this field, Dr. Phelps observed that GABA is not packed into vesicles within pancreatic beta cells; rather, it is spread evenly throughout the beta cell. Finding that GABA was not secreted from vesicles in the beta cell, Dr. Phelps and his colleagues sought another pathway for the release of GABA from the beta cell.

“There is a channel between the interior of the beta cell and the extracellular space, which we thought was worth investigating,” Phelps said. “The volume regulatory anion channel (VRAC) is known for another purpose. It is used to help cells maintain their shape by keeping the osmotic pressure inside and outside the cell in equilibrium. When this balance is disturbed and the cell shape changes, small organic chemicals known as osmolytes are expelled from the cell via the VRAC channel to help the cell regain its shape. When we artificially opened this channel in beta cells using low saline, we found that this channel also transports GABA.”

The researchers used a combination of high performance liquid chromatography (HPLC) and GABA biosensor cell assays to measure the dynamics of GABA release from human islets. In a series of experiments using hypotonic saline to open the VRAC channel, a biosensor was placed downstream from pancreatic islets containing beta cells. The biosensor fluoresced when GABA was released and was viewed via confocal microscopy.

From their research, Dr. Phelps and his colleagues were able to show that, in the human pancreatic islet (beta cell):
  1. GABA is released independently of glucose concentration and in pulses that occur with a frequency in the same range as those of pulsatile in vivo insulin secretion;
  2. GABA is a diffusible factor acting on GABA receptors whose activation regulates beta cell activity (autocrine signaling); and
  3. GABA production and release can regulate the intervals of insulin secretion.

These findings represent a previously undescribed mode of autocrine signaling in the islet that may also extend to many other cell types and tissues known to utilize GABA signaling. “As other researchers build on what we have done and show reproducible results, we will open up totally new areas of biomedical research that scientists can investigate, including possible new treatments for diabetes and potential defense against autoimmune activity,” Phelps concluded.

“Publication of these results in one of the most prestigious journals in the field, Nature Metabolism, is a major accomplishment that illustrates the importance and peer respect for the research that is being conducted by Dr. Phelps and his colleagues. Through interdisciplinary collaborations such as this, faculty in University of Florida Biomedical Engineering are pushing the boundaries of scientific and technological advances underpinning medical innovations that impact us all,” commented Christine Schmidt, Ph.D., professor, J. Crayton Pruitt Family Chair and Department Chair, J. Crayton Pruitt Family Department of Biomedical Engineering.

Forrest Masters, Ph.D., Associate Dean for Research and Facilities at the Herbert Wertheim College of Engineering, remarked, “In our efforts to continue to grow as one of the leading universities in the nation, the Herbert Wertheim College of Engineering has been recruiting talented early career faculty like Dr. Phelps to make critical impacts in engineering, science and medicine. His work with GABA release pathways is one example of how we are bringing new discoveries and innovations that continue to shape the future of healthcare.”

*This project was a collaboration between teams led by Dr. Edward Phelps at the University of Florida, Dr. Alejandro Caicedo at the University of Miami, and Dr. Steinunn Baekkeskov at the Swiss Federal Institute of Technology in Lausanne, Switzerland (EPFL). The research was funded by the National Institutes of Health and JDRF (a nonprofit organization that funds type 1 diabetes research), as well as other funding sources acknowledged in the main research article. The co-first author on the published paper, postdoctoral fellow Dr. Danusa Menegaz from the University of Miami, is currently at São Paulo State University (UNESP) in Brazil. Drs. Phelps, Caicedo and Baekkeskov serve as the corresponding authors.

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