Cancer Center Archives - Page 5 of 11 - Sanford Burnham Prebys

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Institute News

How cancer research silos perpetuate inequity in cancer outcomes: An interview with Svasti Haricharan

AuthorMiles Martin
Date

April 18, 2023

Svasti Haricharan, PhD

The National Institutes of Health recognizes National Minority Health Month each April. This is a time to raise awareness about the importance of reducing the health disparities faced by racial and ethnic minorities.

For our part, we spoke to Assistant Professor Svasti Haricharan, PhD, about her recently published review in Clinical Cancer Research. The paper describes some of the shortfalls of the current research focusing on cancer disparities. It also reveals what needs to happen to solve this problem. 

This paper describes “research silos” in cancer disparities, but what does this term mean?
The cancer research community has made a lot of progress recognizing that cancer research has a data diversity problem. We know that we need more researchers working on cancer disparities—for example, finding explanations as to why some racial and ethnic minorities have worse cancer survival rates than others. We also know that we need to generate more inclusive data in cancer research generally, which means building databases that include data from people of different backgrounds.

However, what we’re talking about in this new paper is a bit more subtle than that. It has more to do with which disparities researchers are studying and how they’re studying them. Cancer-disparities researchers tend to fall into two different categories with two very different approaches. One group focuses more on the societal problems driving disparities, and the other group is looking closely at the biology. But these two paths aren’t intersecting, which is preventing us from truly addressing racial disparities in cancer.

Can you tell us more about those two groups and how this division affects cancer research?
The first group includes researchers who study cancer disparities in the way most people understand them. They focus on social determinants of health, such as socioeconomic status and systemic bias in the healthcare system. The second group looks at the biology directly, focusing on how genetics impacts the molecular biology of cancer. These are both important research areas, and we’ve made a lot of progress independently with each of them.

The problem is that focusing on one or the other ignores something critical that has gained attention in recent years: lifestyle factors have a direct impact on the molecular biology of cancer. Our lived experiences leave a unique footprint in our cells on top of what’s already there because of what we inherited at birth. By keeping these two types of cancer research trapped in silos, we’re missing synergistic leaps that could truly transform our understanding of cancer outcome inequity. Breaking down these silos is the only way to keep moving this type of research forward.

How can we break down these silos? 
Looking at it broadly, funding bodies need to invest more in research that develops datasets using biological samples from underrepresented groups. This will help us learn more about how societal factors can have a different impact on the biology of cancer—depending on the person with the disease. Here in the lab, we need to create experimental systems that better represent the biology of people from racial and ethnic minorities. This could also help us solve an even bigger problem.

Therapeutic strategies for cancer that we find in the lab don’t often make it to the clinic. Improving the diversity of our cancer data will improve this success-to-failure ratio. It will help us identify treatments that work better in some people than in others and choose the best treatments for each patient. In other words, it will help us work toward truly individualized medicine. Ultimately, we can only develop good precision medicine for cancer when we start looking at all patient demographics more equitably.

Institute News

Behind the scenes at Sanford Burnham Prebys’ Cancer Center

AuthorMiles Martin
Date

March 28, 2023

A scientist - a young woman with glasses - presents her poster on colorectal cancer to a group of interested open house guests

Cancer Center open house connects San Diego community with scientists working toward cancer cures

The Institute’s NCI-designated Cancer Center hosted an open house to showcase the latest research advances in cancers of the digestive system. The event was sponsored by the center’s Community Advisory Board (CAB), which provides a link to community networks of people—including patients, survivors and their loved ones.

“These events are especially helpful for people affected by cancer because our researchers can explain the science behind the disease and the approaches we use to find new treatments,” says Associate Professor Cosimo Commisso, PhD, who co-hosted the event with Adjunct Associate Professor Pamela Itkin-Ansari, PhD “As researchers, it’s critical that we have community participation to influence our research—so we benefit as well.” 

The open house, which was free to the public, fulfills a key part of the CAB’s mission—to create awareness of the cancer research being done at the Institute and to promote dialogue between its scientists and the community. Guests had the chance to mingle with cancer researchers, and there was also a panelist table, where they could ask questions directly to a panel including two cancer survivors and a clinician.

The theme of the open house was cancers of the digestive system, which includes pancreatic cancer, liver cancer, stomach cancer and colorectal cancer. Although these cancers are very diverse, one thing many cancers of the digestive system have in common is that they take a long time to diagnose and are difficult to treat. 

“These are devastating cancers,” says Commisso. “We’ve doubled the survival rates for pancreatic cancer since I started working in this field over a decade ago, but it’s still only around 10%. And that’s just not good enough.”

Attendees also got behind-the-scenes tours of labs, including Commisso’s, where researchers are working to halt pancreatic cancer by blocking nutrients—in essence, starving tumor cells of the fuel they need to grow and proliferate. 

“We have a lot of researchers taking different approaches to cancer here at the Institute, and it’s important for people affected by cancer to know that while we’re still a long way off from ending cancer forever, we’re still making progress,” adds Commisso.

Institute News

Padres Pedal the Cause 2023: Team Sanford Burnham Prebys raises $50,000 for cancer research

AuthorMiles Martin
Date

March 20, 2023

Group photo of Team Sanford Burnham Prebys 2023

Team Sanford Burnham Prebys hit the pavement this weekend for Padres Pedal the Cause, an annual fundraising event that invites participants to cycle, spin, run or walk to support local cancer research. The funds raised through each year’s race go to seed grants that fund collaborative cancer research projects in San Diego.

“Padres Pedal the Cause is a chance for the cancer community to come together and remember why collaboration is so important in cancer research,” says bike rider Ze’ev Ronai, PhD, director of the Institute’s NCI-designated Cancer Center. “Virtually all of us know somebody who has been impacted by cancer, including me. This is my fifth Padres Pedal the Cause, and every year I’m so proud to be part of our Institute’s team and help contribute to cancer research outside the lab.”

This year’s team was formidable: 56 employees and friends of the Institute signed up to either ride, run, or walk in the event. Team members came from all areas of the Institute, including faculty, staff scientists, administrative staff, postdocs, and even current and former members of the Institute’s Board of Trustees, such as Bill Gerhart and Steve Williams. Other notable names on this year’s team included longtime participants such as Professor Nicholas Cosford, PhD and James Short, associate director of Digital Communications and Design. 

“I’ve been with Padres Pedal the Cause since the very beginning, and it’s one of the highlights of my year,” says Short, who has helped lead the Institute’s team for the last 10 years.

The team also included some new members this year, such as Assistant Professor Lukas Chavez, PhD, and Director of Experimental Pharmacology Raghu Ramachandra, PhD, who both joined the Institute late last year. 

While Institute employees were well represented on this year’s team, there were also current some of the team’s top fundraisers had a different reason to join team Sanford Burnham Prebys. Kim McKewon is a longtime donor to the Institute and has been participating in Padres Pedal the Cause since its inception in 2013. This year she raised more than $6,000; and to date, she has raised more than $30,000. 

“I pedal for my husband, Ray, who is in remission from leukemia because of science and research, the very focus of the grants that are given from the fundraising that comes out of this event,” she writes in her website bio.

It’s not too late to support Team Sanford Burnham Prebys
To date, team Sanford Burnham Prebys has raised more than $300,000 through Padres Pedal the Cause since its inception in 2013. And while this year’s ride is over, there is always time to support local cancer research. The fundraising deadline for this year’s Padre’s Pedal the Cause is April 18, and 100% of every dollar raised goes toward lifesaving cancer research. Help team Sanford Burnham Prebys create a world without cancer.

Support Team Sanford Burnham Prebys

 

 

Institute News

Sanford Burnham Prebys researchers awarded Curebound grants

AuthorMiles Martin
Date

March 20, 2023

Aninyda Bagchi, PhD, Linda Bradley, Lukas Chavez, PhD, Nicholas Cosford, PhD, and Michael Jackson, PhD

Each year, Sanford Burnham Prebys joins Padres Pedal the Cause, an annual fundraising event that raises money for Curebound which awards collaborative cancer grants in the San Diego area.

These grants include Discovery Grants, which provide seed funds for high-risk/high-reward research in the earliest phases, and Targeted Grants, which are larger awards ($500K) that help translate promising discoveries into treatments for the clinic.

In the 2022-2023 Curebound Research portfolio, five researchers from Sanford Burnham Prebys were awarded grants: Associate Professor Anindya Bagchi, PhD, Professor Linda Bradley, PhD, Assistant Professor Lukas Chavez, PhD, Professor Nicholas Cosford, PhD, and Professor Michael Jackson, PhD

2022 Discovery Grant: Treating incurable pediatric brain tumors 
Bagchi and Chavez will collaborate to advance a new therapeutic approach for medulloblastoma, the most common childhood brain tumor. They will be focusing on a gene called MYC, found only in the deadliest forms of medulloblastoma. This form of brain cancer is currently untreatable, but Bagchi and Chavez recently discovered a molecule that can help control the activity of the MYC gene and potentially inhibit the growth of medulloblastoma tumors. The researcher holds promise to reveal a new treatment approach for this incurable cancer. 

The grant is titled “Decoding the Role of the Long Non-Coding RNA PVT1 in Medulloblastoma.”

2023 Targeted Grant: Discovering a new immunotherapy drug for melanoma
Bradley will be working with Soo Jin Park, MD, from UC San Diego Health to advance a new immunotherapy approach for malignant melanoma. Despite recent advances, this type of skin cancer still causes thousands of deaths in the U.S. each year. The goal of their project is to develop a new drug for melanoma that can reactivate the tumor-killing properties of the patient’s own immune system. This therapeutic approach has the potential to destroy tumors that are resistant to existing therapies, which could help save lives.

The grant is titled, “Advancing Immune Checkpoint Inhibition of PSGL-1 for Treatment of Malignant Melanoma.
 

2022 Discovery Grant: Developing drugs for bone-metastatic prostate cancer
Cosford will work with Christina Jamieson, PhD, from the University of California, San Diego, to advance a new treatment approach for prostate cancer that has spread to the bones. Bone is the most common place for prostate cancer to metastasize, and this form of cancer is currently incurable. The researchers will look for drugs that can kill tumor cells by inhibiting autophagy, a process that promotes tumor progression. The results of the study could identify a new drug ready for clinical trials.

The grant is titled “Pre-Clinical Development of New Autophagy Targeting Drugs for Bone Metastatic Prostate Cancer.”

2022 Discovery Grant: Repurposing drugs for deadly childhood brain cancer
Jackson and Chavez will collaborate to identify new treatment options for ependymoma, an aggressive pediatric brain tumor and leading cause of death among childhood cancer patients. The researchers will screen patient tumor cells against drugs already approved by the FDA for other conditions, looking for drugs that could be repurposed to fight these tumors. Because FDA-approved drugs are known to be safe for humans, this may prove to be the quickest way to help patients currently living with this cancer. 

The grant is titled “High Throughput-Screen for Inhibitors of Pediatric Ependymoma.”

Institute News

Is cloud computing a game changer in cancer research? Three big questions for Lukas Chavez

AuthorMiles Martin
Date

February 22, 2023

Lukas Chavez, PhD

As an assistant professor at Sanford Burnham Prebys and director of the Neuro-Oncology Molecular Tumor Board at Rady Children’s Hospital, Lukas Chavez, PhD, leverages modern technology for precision diagnostics and for uncovering new treatment options for the most aggressive childhood brain cancers.

We spoke to Chavez about his work and asked him how modern technology—particularly cloud computing—is shifting the approach to cancer research.

How are you using new technologies to advance your research?

New technologies are helping us generate a huge amount of data as well as many new types of data. All this new information at our disposal has created a pressing need for tools to make sense of it and maximize their benefits. That’s where computational biology and bioinformatics come into play. The childhood brain cancers I work on are very rare, which has historically made it difficult to study large numbers of cases and identify patterns.

Now, data for thousands of cases can be stored in the cloud. By creating data analysis tools, we can reveal insights that we would never have seen otherwise. For example, we’ve developed tools that can use patient data in the cloud to categorize brain cancers into subtypes we’ve never identified before, and we’re learning that there are many more types of brain tumors than we’ve previously understood. We’re basically transforming the classic histo-pathological approach that people have studied for decades by looking at tumor tissues under the microscope and turning that into data science.

How is cloud computing improving cancer research in general?

Assembling big datasets delays everything, so I believe the main idea of cloud computing is really to store data in the cloud, then bring the computational tools to the data, not the other way around.

My team did one study where we assembled publicly available data, and basically downloaded everything locally. The data assembly process alone took at least two to three years because of all the data access agreements and legal offices that were involved.

And that is the burden that cloud computing infrastructures remove. All of this personalized cancer data can be centrally stored in the cloud, which makes it available to more researchers while keeping it secure to protect patient privacy. Researchers can get access without downloading the data, so they are not responsible for data protection anymore. It’s both faster and more secure to just bring your tools to the data.

Are there any risks we need to be aware of?

Like any new technology, we need to be clear about how we use it. The technology is another tool in the toolbox of patient care. It will never entirely replace physicians and researchers, but it can complement and assist them.

Also, because we use costly and sophisticated tools that are being built and trained on very specific patient groups, we need to be careful that these tools are not only helping wealthier segments of society. Ideally, these tools will be expanded worldwide to help everybody affected by cancer.

Institute News

How community collaboration shapes leukemia research at Sanford Burnham Prebys

AuthorMiles Martin
Date

October 4, 2022

Rena Johnson, Ani Deshpande, PhD, and Todd Johnson holding a large cardboard check for $25,000 from the Luke Tatsu Johnson Foundation

Since 2020, Todd and Rena Johnson, co-founders of the Luke Tatsu Johnson Foundation (LTJF), have helped fund the research of Associate Professor Ani Deshpande, PhD

But it all started with their son Luke. He had a very rare subtype of acute myeloid leukemia, one of the most difficult-to-treat cancers, and, sadly, he passed away from the disease in 2016. This inspired the Johnsons to become involved with fundraising and advocacy for cancer research.

“Our foundation started with a fundraising golf tournament to honor Luke, and that was about taking something so horrific and so horrible and finding a way to turn it into something positive,” says Rena. “If you can take that tragedy and put a positive spin on it, then everything around Luke and his name and his memory becomes positive.”

How “the stars and planets aligned” to bring the Johnsons to the Institute

In a remarkable coincidence, the Johnsons discovered on their first visit to the Institute that Deshpande’s research focuses on AF10 fusion AML, an extremely rare subtype of the disease that accounts for about 5 percent of cases. It’s also the subtype of AML that Luke had.

“It was a goosebumps-raising moment,” says Todd. “Once we visited Ani and saw his lab, we realized there was a lot more in common with our story and his research than we had realized before.”

“The stars and planets aligned and brought us to Ani,” adds Rena. 

Luke Tatsu Johnson

Luke Tatsu Johnson

As well as helping fund Deshpande’s research through LTJF and their partnership with the Rally! Foundation, the Johnsons are also on the Community Advisory Board (CAB) for the Institute’s Cancer Center, which advocates for cancer research by engaging the community. 

“The CAB does such a wonderful job of connecting the community with the scientists, and we’re so excited to be involved in that,” says Todd. “That’s fundamentally what we do as a foundation—we support the folks doing this work so that children and families down the road can have a different outcome from Luke’s.”
 

AML research “needs more support and needs more funding”

The Johnsons’ support helped the AML research team discover a new potential treatment for AML, which is currently in preclinical studies, after which they hope it will advance to clinical trials. The research team maintains that it would have been impossible to secure the NIH grants necessary to do these studies without the jump start given by the LTJF and the Rally! Foundation.

“We couldn’t do what we do without the Johnsons’ support,” says Deshpande. “We are so grateful to have them in our corner, and we’re confident that our work will help improve outcomes for kids like Luke down the line.”

Despite this progress, more research into AML and other leukemias is still needed. Leukemia is the most common cancer in children and teens. About 4,000 children are diagnosed with leukemia each year, and AML accounts for about a third of these cases.
 

Studying AML from all angles

To tackle this pressing problem, the Institute has established an AML disease team composed of researchers across labs and clinician partners. The team’s research falls into several large categories, including studying the genetics of AML, studying how the disease works in animal models and working to develop drugs that can target specific mutations associated with the disease, which are numerous. 

“AML has many different subtypes, so it’s been difficult for researchers to make major advances to treat all cases of AML,” says Deshpande, who co-leads the AML team with Professor Peter D. Adams, PhD “Most patients with AML are given the same treatments that have been used since the ’70s, which is why we want to look at AML from as many angles as possible.”

In addition to being difficult to treat, it is also challenging to get funding for AML research, particularly for the rarer subtypes. This makes the support of foundations such as LTJF even more vital to researchers like Deshpande. 

“This is exactly why AML research needs more support and needs more funding, because this is a much more difficult disease than other forms of leukemia,” says Todd. “Many patients don’t have positive outcomes, and the only way to turn that pendulum is to intensify our efforts and increase the amount of research being done.”

Institute News

Heating up cold brain tumors: An emerging approach to medulloblastoma

AuthorMiles Martin
Date

July 6, 2022

Cancer cells

Immunotherapy has revolutionized cancer treatment, but it doesn’t work on many childhood brain tumors. Researchers from Sanford Burnham Prebys are working to change that.

Brain tumors account for about a quarter of all cancer cases in children. Medulloblastoma, a particularly aggressive form of childhood brain cancer, often develops resistance to radiation and chemotherapy. Researchers from Sanford Burnham Prebys are working to solve this problem by harnessing the power of the immune system.

They describe the potential of this approach in their recently published paper in Genes & Development. 

“The brain’s location makes it very difficult to target medulloblastoma tumors with current therapies,” says first author Tanja Eisemann, PhD, a postdoctoral associate in the lab of Robert Wechsler-Reya, PhD “They’re also immunologically cold, which means they’re good at evading the immune system.” 

The researchers hypothesize that it may be possible to enhance the body’s immune response to medulloblastoma and help the body’s immune cells enter the brain, making treatment with immunotherapy possible.

“Immunotherapy has so much potential as a  cancer treatment, but its scope is limited right now,” says Eisemann. “We want to bring the benefits of this therapy to medulloblastoma patients and their families.”

Eisemann has been studying this approach in mice, and although the research is still at an early stage, she and her colleagues are highly optimistic about its potential.

“The brain has long been considered immune privileged, hidden from immune-system surveillance and immune responses. But we’re starting to see that this isn’t the case,” says Eisemann. “This is a rapidly evolving field, and I’m excited to be working in a lab on the forefront of that research.”

Institute News

Three Sanford Burnham Prebys faculty receive promotions

AuthorMiles Martin
Date

June 30, 2022

Ani Deshpande, Brooke Emerling and Charles Spruck

Sanford Burnham Prebys is proud to announce the promotion of three of our faculty from assistant to associate professor. 

The promoted faculty, all from the Institute’s NCI-designated Cancer Center, include Ani Deshpande, PhD, Brooke Emerling, PhD and Charles Spruck, PhD

Ani Deshpande, PhD

Deshpande studies developmental processes in stem cells that get hijacked by cancer, focusing specifically on acute myeloid leukemia, one of the most common types of blood cancer. Earlier last year, Deshpande published a study with researchers at the National Institutes of Health (NIH) revealing that CRISPR gene editing can sometimes favor cells with cancer mutations, encouraging a cautious approach when using CRISPR therapies for certain cancers

Deshpande joined the Institute in 2015. Prior to that, he held positions at Memorial Sloan Kettering Cancer Center and Harvard Medical School.

Brooke Emerling, PhD

Emerling studies the metabolism of cancer cells, specifically how certain signaling proteins can contribute to the uninhibited growth typical of tumors. Emerling recently received a $2.3 million grant from the NIH to continue her work over the next four years.

Emerling joined the faculty at Sanford Burnham Prebys in 2016. Prior to that, she held positions at Weill Cornell Medicine and Harvard Medical School.

Charles Spruck, PhD 

Spruck develops new, effective, nontoxic treatments for patients with advanced cancers. Specifically, his recent studies have focused on the potential to treat cancer with viral mimicry, which tricks the body into thinking it has a viral infection, stimulating immune responses that can help the body fight cancer and improve the effects of other treatments. 

Spruck joined the Institute in 2010. Prior to that, he held positions at the Sidney Kimmel Cancer Center and Scripps Research.

Institute News

Fishman Fund Fellowship awarded to Cynthia Lebeaupin for liver cancer research

AuthorMiles Martin
Date

June 8, 2022

Cynthia Lebeaupin, PhD

Cynthia Lebeaupin, PhD was recently awarded the 2022 Fishman Fund Fellowship, a postdoctoral award unique to Sanford Burnham Prebys.

The award provides a boosted stipend to exceptional postdocs from the Institute who have a demonstrated research track record and whose work shows significant potential for future breakthroughs.

“It’s an honor to have been selected for such a prestigious award from the Institute, says Lebeaupin, who works in the lab of Randal J. Kaufman, PhD “The resources and people at Sanford Burnham Prebys are incredible and I’m happy to be able to continue my research here.”

Sanford Burnham Prebys introduced the Fishman Fund Awards in 2001 to honor of the Institute’s founders, Dr. William and Lillian Fishman. The fund was established by Reena Horowitz and the late Mary Bradley, longtime supporters of the Institute.

“The Fishmans created an Institute that fosters a collaborative, inspirational atmosphere for postdoc students,” said Horowitz at the 2021 Fishman Fund Awards. “The Fishmans understood that support for new science is a brilliant research investment.”

Lebeaupin has been at the Institute since 2018, and this is not her first honor from the Fishman Fund. In 2021, she was awarded a Fishman Fund Career Development Award, a smaller prize offered to several postdocs each year. She also completed an internship at the Institute’s former Lake Nona campus in 2014.

“I’ve had an affinity for Sanford Burnham Prebys for a long time,” says Lebeaupin. “I knew once I met Dr. Kaufman and everybody on campus that this was the best place to complete my postdoc.”

Lebeaupin’s research focuses on a growing and pressing problem in medicine – liver cancer. One of the major risk factors for developing liver cancer is fat accumulation in the liver, known as fatty liver disease. Increases in obesity rates over the last several decades have led to a dramatic increase in fatty liver disease.

Fatty liver disease is increasing at an alarming rate, and unfortunately, it’s here to stay,” says Lebeaupin. “My research is figuring out how fatty liver disease progresses to liver cancer, so we can use this knowledge to help prevent it.” 

In particular, Lebeaupin is working on exploring how cells respond to fatty liver disease over time. She discovered that a molecule that helps liver cells protect themselves from short-term stress can promote cancer in the long-term. She has now moved into studying the system in human tissues.

“This research is exciting because we aim to translate our discoveries from the bench to the bedside,” says Lebeaupin. “What I hope to do in the future is use new technologies on liver samples from patients so we can identify what’s actually going on in liver diseases.”

Institute News

Facing cancer disparities head-on: An interview with Svasti Haricharan

AuthorMiles Martin
Date

May 25, 2022

Svasti Haricharan, PhD

Svasti Haricharan, PhD, and her lab are revealing why more Black women get breast cancer, and they’re also telling us what we can do about it. 

Svasti Haricharan, PhD, an assistant professor at Sanford Burnham Prebys, is tackling one of the most pernicious problems facing cancer researchers today—why some people, particularly disenfranchised groups such as Black women, get cancer more frequently and more severely than others. For years, the answer has been explained away by differences in lifestyle or socioeconomic status, but Haricharan’s research, published in Therapeutic Advances in Medical Oncology, is demonstrating that the real answer is much more complicated. 

What were your findings?
We found differences between the breast cells of white and Black women that help explain why Black women experience higher mortality from ER+ breast cancer. These included differences in the expression of specific genes and consistent molecular differences in the cellular signals controlling how fast cells can grow. These differences were present in both healthy and cancerous cells. 

Why is it important to study breast cancer disparities?
Black and white women have about the same incidence of ER+ breast cancer, but Black women are 42% more likely to die from it. This is just one example of the type of glaring health disparity we see in Black people and other marginalized communities. Unfortunately, these issues have been severely neglected by the research community. Or worse still, they are attributed entirely to lifestyle factors, which often shift the blame to the patients themselves. 

What do your findings mean for women with breast cancer?
The immediate implication is that we can act on this information to improve diagnostics and treatment for Black women with breast cancer. Our results suggest that at least some Black women could benefit from being treated earlier with CDK inhibitors, which are drugs we already have and understand. In the bigger picture, we’re showing that there are internal factors at play in health disparities that develop based on people’s lived experiences. We’re going to have to really dive in and explore these factors if we want to make any real progress in precision medicine. Everybody deserves care that is tailored to their molecular makeup as closely as possible.

What are some of the challenges still facing researchers working on health disparities?
The simplest answer is getting the money to do the research. We’re fortunate that we’ve found something here that’s quickly actionable, but it’s not always going to work out like that. This isn’t about just a few more studies. The types of differences we’ve found here are likely present in other types of cancer and in other groups. The more we look, the more we’re going to find. Funders and researchers alike need to be willing to prioritize this type of research going forward, or we’ll never see real change.