Research Area: Immunology

New faculty join the School of Science in 2022

Seven professors join the departments of Biology; Chemistry; Earth, Atmospheric and Planetary Sciences; Mathematics; and Physics.

School of Science
November 17, 2022

This fall, the MIT School of Science welcomes seven new faculty to the departments of Biology; Chemistry; Earth, Atmospheric and Planetary Studies (EAPS); Mathematics; and Physics.

Wanying Kang researches large-scale atmospheric and oceanic dynamics, and their effects on the climate of Earth and other planetary bodies. She hopes to bridge multiple geoscience fields by applying tools from climate science on Earth to planetary science questions. Currently, Kang is looking into the atmospheric circulation on superhot lava worlds and the ocean circulation on icy moons, given the potential to observe them in more detail in the near future.

Kang earned an undergraduate degree in physics from Peking University and a PhD in applied math from Harvard University. She first joined the Department of Earth, Atmospheric and Planetary Sciences as a distinguished postdoc through the Houghton-Lorenz Fellowship. Now, Kang has been appointed an assistant professor in climate science in EAPS.

Sarah Millholland explores the demographics and diversity of extrasolar planetary systems. Using orbital dynamics and theory, she investigates how gravitational interactions like tides, resonances, and spin dynamics influence the formation and evolution of planetary systems and shape observable exoplanet properties.

Millholland obtained bachelor’s degrees in physics and applied mathematics from the University of Saint Thomas in 2015. She spent her first year of graduate school at the University of California at Santa Cruz before transferring to Yale University, earning her PhD in astronomy from Yale in 2020. She then moved to Princeton University, where she was a NASA Sagan Postdoctoral Fellow from 2020-22. Millholland joins MIT as an assistant professor in the Department of Physics and a member of the Kavli Institute for Astrophysics and Space Research.

Sam Peng PhD ’14 aims to develop novel probes and microscopy techniques to visualize the dynamics of individual molecules in living cells, which will improve the understanding of molecular mechanisms underlying human diseases. Peng’s group will focus on studying molecular dynamics, protein-protein interactions, and cellular heterogeneity involved in neurobiology and cancer biology. Their long-term goal is to translate these mechanistic insights into drug discovery.

Peng received his bachelor’s degree in chemistry from the University of California at Berkeley, and his PhD from MIT in physical chemistry. Most recently, he completed postdoctoral research at Stanford University. He returns to MIT as an assistant professor in the Department of Chemistry and a core member of the Broad Institute of MIT and Harvard.

Julien Tailleur is a physicist focusing on the emerging properties of active materials, which encompass systems made of large assemblies of units able to exert propelling forces on their environment. From molecular motors to cells and animal groups, active systems are found at all scales in nature. Most recently, Tailleur combined the development of theoretical frameworks to describe active systems with their applications to the study of microbiological systems.

Tailleur completed his undergraduate studies in mathematics at Université Pierre et Marie Curie (UPMC) and in physics at Université d’Orsay. He earned his PhD in physics in 2007 from UPMC. After becoming an Engineering and Physical Sciences Research Council postdoc at the University of Edinburgh, Tailleur joined French National Centre for Scientific Research (CNRS) and Université Paris Diderot in 2011, then becoming a CNRS Director of Research in 2018. Tailleur joins the Department of Physics as an associate professor.

Richard Teague works to understand the earliest stages of planetary systems, specifically, where, when, and how they can form. A major component of his research is the development of new techniques to detect examples of planets while they are still embedded in their parental protoplanetary disks, a period of the planet’s growth phase which is currently hidden from view. Teague is also leading the exoALMA collaboration, searching for the youngest exoplanets with one of the largest telescopes in the world, the Atacama Large (sub-) Milimeter Array (ALMA).

Teague earned a master’s degree from the University of Edinburgh and a PhD from the Max-Planck-Institute for Astronomy. Previously, he was a Submillimeter Array fellow at the Harvard-Smithsonian Center for Astrophysics and a postdoc at the University of Michigan and the Max-Planck-Institute for Astronomy. Teague joins MIT as an assistant professor in the Department of Earth, Atmospheric and Planetary Sciences.

Research interests of Martin Wainwright PhD ’02 include high-dimensional statistics, statistical machine learning, information theory, and optimization theory. One focus is algorithms and Markov random fields, a class of probabilistic model based on graphs used to capture dependencies in multivariate data: for example, image models, data compression, and computational biology. He also studies the effect of decentralization and communication constraints in statistical inference problems. A final area of interest is methodology and theory for high-dimensional inference problems.

Wainwright received a bachelor’s degree in mathematics from University of Waterloo followed by a PhD in electrical engineering and computer science (EECS) from MIT. Most recently, he was the Chancellor’s Professor at the University of California at Berkeley with a joint appointment between the departments of Statistics and EECS. Wainwright returns to MIT as a professor of mathematics and electrical engineering and computer science.

Immune cells communicate across scales in time and space, forming circuits that control their destructive capacity. Harikesh Wong employs a variety of quantitative approaches, including advanced fluorescence microscopy and computational modeling, to study these circuits within intact tissue environments. Ultimately, he seeks to understand how imbalanced immune cell communication — due to genetic or environmental variation — results in detrimental outcomes, including chronic infection, autoimmunity, and the formation of tumors.

Wong received a bachelor’s degree from McMaster University followed by a PhD in cell biology from the University of Toronto. Next, he pursued a postdoc at the National Institutes of Health in immunology and systems biology. Wong joins MIT as an assistant professor in the Department of Biology and a core member of the Ragon Institute of MGH, MIT and Harvard.

Yiyin Erin Chen and Sam Chunte Peng named as core members of Broad Institute and MIT
Broad Communications
July 12, 2022

Broad Institute of MIT and Harvard has named Erin Chen, a dermatologist and microbiologist, and Sam Peng, a biophysicist and physical chemist with expertise in single-molecule imaging, as core institute members.

Chen will join in January 2023 and will also serve as an assistant professor in the Department of Biology at MIT and an attending dermatologist at Massachusetts General Hospital. Peng joined in July 2022 and will serve as an assistant professor in the Department of Chemistry at MIT.

Chen’s lab will study the communication between the immune system and the diverse microbes that colonize every surface of the human body, with a focus on the human body’s largest organ, the skin.

Peng’s lab will develop novel probes and microscopy techniques to visualize the dynamics of individual molecules in living cells, which will improve the understanding of molecular mechanisms underlying human diseases.

“We are delighted to welcome Sam and Erin to the Broad community,” said Todd Golub, director of the Broad. “These creative scientists are each taking inventive approaches to understand the molecular signals and interactions that underlie biological processes in health and disease. These insights will help further the Broad’s mission of advancing the understanding and treatment of human disease.”

Erin Chen.
Erin Chen

Erin Chen earned her BA in biology from the University of Chicago, her PhD from MIT, and her MD from Harvard Medical School. Prior to joining the Broad, Chen was a Howard Hughes Medical Institute Hanna Gray Postdoctoral Fellow at Stanford University, in the lab of Michael Fischbach. She was also an attending dermatologist at the University of California San Francisco and at the San Francisco VA Medical Center. During her postdoctoral research, Chen developed genetic methods to study harmless commensal skin bacteria. She engineered these bacteria to generate anti-tumor immunity, pioneering a novel approach to vaccination and cancer immunotherapy.

At the Broad, members of the Chen lab will continue to employ microbial genetics, immunologic approaches, and mouse models to dissect the molecular signals used by commensal microbes to educate the immune system. Ultimately, Chen aims to harness these microbe-host interactions to engineer novel therapeutics for human disease.

“I’m excited to join the collaborative scientific community at the Broad and MIT, including those who have pioneered novel tools for examining biological mechanisms at higher spatial resolution,” said Chen. “The biology I study is quite basic, but I’m motivated by the potential impact it could have on patients. Figuring out how commensal skin bacteria are captured by the immune system could unlock a whole new therapeutic toolbox.”

Sam Peng
Sam Peng

Sam Peng earned his BS in chemistry from the University of California, Berkeley, and his PhD from MIT in physical chemistry. He completed his postdoctoral research at Stanford University as an NIH K99 Pathway to Independence scholar in the lab of Steve Chu. During his postdoctoral research, he developed long-term single molecule imaging in live cells using a novel class of nanoprobes. He applied this new technique to study axonal transport in neurons and the molecular dynamics of dynein — a motor protein involved in transporting cargo in cells.

At the Broad, the Peng group will aim to elucidate the molecular mechanisms underlying human diseases. Lab members will develop and integrate a diverse toolbox spanning single-molecule microscopy, super-resolution microscopy, spectroscopy, nanomaterial engineering, biophysics, chemical biology, and quantitative modeling to uncover previously unexplored biological processes. With bright and photostable probes, lab members will have unprecedented capability to record ultra-long-term “molecular movies” in living systems with high spatiotemporal resolutions and to reveal molecular interactions that drive biological functions. Peng’s group will focus on studying molecular dynamics, protein-protein interactions, and cellular heterogeneity involved in neurobiology and cancer biology. Their long-term goal is to translate these mechanistic insights into drug discovery.

“Because my research is so multi-disciplinary, joining the Broad and MIT communities allows us to integrate a range of experimental tools and to collaborate with colleagues and students from diverse backgrounds,” said Peng. “I’m excited to see how our techniques can enable discoveries for a variety of cellular processes, including those underlying complex brain functions and dysfunctions. Many problems that previously seemed inaccessible now appear to be within reach in the foreseeable future.”

Yiyin Erin Chen

Education

  • Graduate: PhD, 2011, MIT; MD, 2013, Harvard Medical School
  • Undergraduate: BA, 2006, Biology, University of Chicago

Research Summary

Diverse commensal microbes colonize every surface of our bodies. We study the constant communication between these microbes and our immune system. We focus on our largest organ: the skin. By employing microbial genetics, immunologic approaches, and mouse models, we can dissect (1) the molecular signals used by microbes to educate our immune system and (2) how different microbial communities alter immune responses. Ultimately, we aim to harness these microbe-host interactions to engineer novel vaccines and therapeutics for human disease.

Awards

  • Howard Hughes Medical Institute Hanna H. Gray Fellow, 2018-2026
  • A.P. Giannini Postdoctoral Research Fellowship, 2018
  • Dermatology Foundation Research Fellowship, 2017
Alison E. Ringel

Education

  • PhD, 2015, Johns Hopkins University School of Medicine
  • BA, 2009, Molecular Biology & Biochemistry/Physics, Wesleyan University

Research Summary

We investigate crosstalk between CD8+ T cells and their environment at a molecular level, by dissecting the biological and metabolic programs engaged under conditions of stress. Using an array of approaches to model and perturb the local microenvironment, our research aims to reveal both the adaptive molecular changes as well as intrinsic vulnerabilities in T cells that arise within the tumor niche. Our goal is to understand how disease states remodel the fundamental mechanisms that regulate immune cell function and contribute to pathogenesis.

Awards

  • Forbeck Scholar, 2021
Harikesh S. Wong

Education

  • PhD, 2016, University of Toronto
  • BSc, 2010, Biochemistry, McMaster University

Research Summary

The immune system mounts destructive responses to protect the host from threats, including pathogens and tumors. However, a trade-off emerges: if immune responses cause too much damage, they can compromise host tissue function. Conversely, if they fail to generate sufficient damage, the host may succumb to a given threat. How is the optimal balance achieved? The Wong lab investigates how cells communicate with one another and their surrounding tissue environment to accurately control the magnitude of immune responses, both in time and space. To this end, we combine the tools of immunology with interdisciplinary methods—including high-resolution fluorescence microscopy, computational approaches, and gene manipulations—to resolve, model, and perturb the control of immune responses in intact tissues. Ultimately, we aim to understand how subtle shifts in control can lead to widely divergent host outcomes, including the successful elimination of threats, tolerance, autoimmunity, chronic infection, and cancer.

Hernandez Moura Silva

Education

  • PhD, 2011, University of São Paulo Heart Institute
  • MSc, Molecular Biology, 2008, University of Brasilia
  • BS, 2005, Biology, University of Brasilia

Research Summary

By utilizing an innovative and intersectional approach, our lab main goal is to reveal fundamental immune-related pathways that modulate organ and tissue physiology. Our work will help to develop new strategies to tune these molecular pathways in health and disease, leading to the development of much-needed therapeutic approaches for human diseases.

Awards

  • CAPES Thesis Award – Brazil, 2012
Vaccine Booster

Biologist Jianzhu Chen works to enhance immune response

Mark Wolverton | Spectrum
November 16, 2020

Jianzhu Chen, professor of biology and a member of the Koch Institute for Integrative Cancer Research at MIT, is pursuing a different strategy from most of his colleagues working on SARS-CoV-2, the virus that causes Covid-19. “We focus on the immune system and fundamental mechanisms as well as their application in cancer immunotherapy, vaccine development, and metabolic diseases,” he explains. Rather than trying to develop a specific vaccine, Chen is pursuing vaccine platform technologies that can be used to enhance any vaccine.

This effort is built on Chen’s previous work on dengue fever, a severe tropical disease transmitted by mosquitos. “We have been working to improve a vaccine against dengue virus infection,” he says, “which has this phenomenon called antibody-dependent enhancement,” in which “non-neutralizing” antibodies bind to the virus but do not destroy it. The immune system’s pathogen-eating macrophages then consume these virus-antibody complexes and become infected themselves, making a subsequent infection worse.

Chen’s team has identified vaccine adjuvants, or enhancing agents, that can increase neutralizing (that is, effective) antibodies while reducing non-neutralizing antibody response in mice and nonhuman primates. The team is confident that using a similar strategy against Covid-19 would improve any vaccine’s effectiveness.

Addressing cytokine storm

Chen is also focusing on the dangerous hyperinflammatory response seen in Covid-19: the cytokine storm that can result when the immune system overreacts to infection.

“We have been working on macrophage biology for quite some time,” Chen says. “SARS-CoV-2 infection is a hyperinflammatory response, and macrophages probably play a critical role in that response.”

“We have identified many compounds, including FDA-approved drugs, bioactive compounds, and natural products that can modulate macrophage activity to become anti-inflammatory,” he says. Such macrophage modulation would likely be used in conjunction with other treatments as a therapeutic strategy for already-infected patients.

A promising result from either research project could be used along with a Covid-19 vaccine to enhance immune response while preventing or reducing the severity of any possible reinfection. But it’s too early to tell what might happen. “We don’t have a vaccine yet,” Chen notes. “It’s not clear when we’ll have one. Even when we have one, it’s not clear how well it will work. It could be 95% protection; it could be 50%. Some of them may not confer much protection at all. But even 50% or 60% is a significant number of people.”

Another challenge, Chen acknowledges, is that medical research must move from theory to lab and ultimately into the real world. Vaccines can be designed and modeled on computers but eventually “we have to test them to see if they work as we expect,” he says. “You have to immunize mice or some other animals and then challenge them with SARS-CoV-2 to see whether the vaccine protects the animals from infection or dramatically minimize disease symptoms. These kinds of studies can’t be modeled computationally.”

Chen also hopes that his particular contributions will have benefits beyond the pandemic. “We’re aiming to develop a vaccine platform prototyped on SARS-CoV-2 that can be used for the development of many other vaccines as well, using the most appropriate technologies.” If that happens, science will have dug at least one substantial jewel out of the depths of an unprecedented public health crisis.

Type 1 diabetes from a beta cell’s perspective
Eva Frederick | Whitehead Institute
September 24, 2020

Type 1 diabetes is an autoimmune disease that occurs when T-cells in the immune system attack the body’s own insulin-producing cells, called beta cells, in the pancreas. Usually diagnosed in children and young adults, type 1 diabetes accounts for around five percent of all diabetes cases.

The underlying biology of type 1 diabetes is tricky to study for a number of reasons. For one thing, by the time a person begins to show symptoms, their T-cells have already been destroying beta cells for a long period — months or even years. Also, the initial trigger for the disease is often unclear; a number of beta cell proteins can set off the immune response.

In a study published Sept. 22 in Cell Reports Medicine, researchers in the lab of Whitehead Institute Founding Member Rudolf Jaenisch demonstrate a new experimental system for more precisely studying the mechanisms of type 1 diabetes, focusing on how a person’s beta cells respond to an attack from their own immune system. In doing so, they reveal features of the disease that could be targets for future therapeutics.

“Here our question was, let’s say the T cells get activated; what happens next from the perspective of beta cells? Could we find some potential intervention opportunities?” said Haiting Ma, a postdoctoral associate in Jaenisch’s lab and the first author of the study.

Ma, working with Jaenisch, also a professor of biology at MIT, and Jacob Jeppesen, Novo Nordisk’s Head of Diabetes and Metabolism Biology, took a synthetic biology approach to achieve this goal.

The researchers engineered a system by inducing human pluripotent stem cells to differentiate into functional pancreatic beta cells, and added a model antigen called CD19 to these cells using CRISPR techniques. They established that these cells functioned as insulin-producing beta cells by implanting them in diabetic mice; upon receiving the cells, the mice experienced an improvement in glucose levels.

They then replicated the autoimmune components of the disease using engineered immune cells called CAR-T cells. CAR-T cells are T-cells tailor-made to attack a certain type of cell; for example, they can be targeted to tumor cells to treat certain types of cancer. For the diabetes model, the researchers engineered the cells to contain receptors for the model antigen CD19.

When the researchers cocultured the synthetic beta cells and CAR-T cells, they found the system worked well to mimic a simplified version of type 1 diabetes: the CAR-T cells attacked the beta cells and caused them to enter the process of cell death. The researchers were also able to implement the strategy in humanized mice.

Using their new experimental system, the researchers were able to identify some interesting factors involved in the beta cells’ response to diabetic conditions. For one thing, they found that the beta cells cranked up production of protective mechanisms such as the protein PDL1. PDL1 is a protein found on non-harmful cells in the body that, in normal circumstances, prevents the immune system from attacking them.

Changes in PDL1 levels had been associated with type 1 diabetes in previous studies. Now, Ma wondered if it was possible to rescue the beta cells from the immune onslaught by inducing the expression of even more of the helpful protein. “We found that we can help beta cells by giving them a higher expression of PDL1,” he said. “When we do this, they can do better in the model.” If validated in human cells, increasing expression of PDL1 could be evaluated as a potential therapeutic method, Ma said.

Another finding concerned the way the cells died after T-cell attack. Ma found that the genes that were being upregulated as the beta cells were under attack were associated not with the usual form of cell death, apoptosis, but with a more inflammatory and violent kind of cell death called pyroptosis.

“The interesting thing about pyroptosis is that it causes the cells to release their contents,” Ma said. “This is in contrast to apoptosis, which is considered to be the main mechanism for autoimmune response. We think that pyroptosis could play a role in propelling this autoimmune reaction, because the contents from beta cells include multiple potential antigens. If these are released, they can be picked out by antigen presenting cells and start to crank up this autoimmunity.”

The process of pyroptosis in the context of beta cell autoimmunity could be linked to ER stress in beta cells, a highly secretory cell type. Indeed, an ER stress inducing chemical increased the marker of pyroptosis.

If researchers could find a way to inhibit the process of pyroptosis safely in humans, it could potentially lessen the severity of the autoimmune reaction that is the hallmark of type 1 diabetes. Pyroptosis is mediated by a protein called caspase-4, which can be inhibited in the lab. “If that can be validated in patient beta cells, that could indicate that modulating caspases could also be [a therapeutic mechanism],” Ma said.

Going forward, Ma and Jaenisch plan to investigate the immune mechanisms underlying autoimmunity in humans by using induced pluripotent stem cells from patients with type 1 diabetes. “These cells could be differentiated into immune cells such as T, B, macrophage, and dendritic cells, and we can investigate how they interact with beta cells,” Ma said.

They also plan to keep improving their new experimental system. “This system provides a very robust and tractable synthetic immune response that we can use to study type 1 diabetes,” said Jaenisch. “In the future it could be used to study other autoimmune diseases.”

This study was supported by a generous gift from Liliana and Hillel Bachrach, a collaborative research agreement from Novo Nordisk, and NIH grant 1R01-NS088538 (to R.J.).

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Written by Eva Frederick

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Citation:

Ma, H., Jeppesen, J, and Jaenisch, R. “Human T-cells expressing a CD19 CAR-T receptor provide insights into mechanisms of human CD19 positive cell destruction.” Cell Reports Medicine. Sept 22. https://doi.org/10.1016/j.xcrm.2020.100097

A Wide Net to Trap Cancer

Stefani Spranger is exploring multiple avenues for the next immunotherapy breakthrough

Pamela Ferdinand | Spectrum
March 12, 2019

A YOUNG LAB AT THE FOREFRONT OF IMMUNOTHERAPY DISCOVERIES is an exciting yet challenging place to be. MIT faculty member Stefani Spranger, an expert in cancer biology and immunology, understands that better than most people.

Spranger knows that new labs such as hers, which opened in July 2017 at the Koch Institute for Integrative Cancer Research at MIT, face distinct advantages and disadvantages when it comes to making their mark. While younger labs typically have startup grants, they lack the long-term funding, track record, and name recognition of established researchers; on the other hand, new labs tend to have smaller, close-knit teams open to tackling a wider array of investigative avenues to see what works, what doesn’t work, and where promise lies.

That’s when the funds and recognition of an endowed professorship can make a big difference, says Spranger, an assistant professor of biology who last year was named the Howard S. (1953) and Linda B. Stern Career Development Professor. “Not everything will work, so being able to test multiple approaches accelerates discovery and success,” she says.

Spranger is working to understand the mechanisms underlying interactions between cancer and the immune system—and ultimately, to find ways to activate immune cells to recognize and fight the disease. Cancer immunotherapies (the field in which this past year’s Nobel Prize in Physiology or Medicine was awarded) have revolutionized cancer treatment, leading to a new class of drugs called checkpoint inhibitors and resulting in lasting remissions, albeit for a very limited number of cancer patients. According to Spranger, there won’t be a single therapy, one-size-fits-all solution, but targeted treatments for cancers depending on their characteristics.

To discover new treatments, Spranger’s lab casts a wide net, asking big-picture questions about what influences anti-tumor immune response and disease outcome while also zooming in to investigate, for instance, specifically how cancer-killing T cells are excluded from tumors. In 2015, as a University of Chicago postdoc, Spranger made the novel discovery that malignant melanoma tumors with high beta-catenin protein lack T cells and fail to respond to treatment while tumors with normal beta-catenin do.

Her lab focuses on understanding lung and pancreatic cancers, employing a multidisciplinary research team with expertise ranging from immunology and biology to math and computation. One of her graduate students is using linear algebra to develop a mathematical model for translating mouse data into more accurate predictions about key signaling pathways in humans.

Another project involves exploring the relationship between homogenous tumors and immune response. Not every cancer cell is identical, nor does it have the same molecules on its surface that can be recognized by an immune cell; cancer patients with a more homogenous expression of those cells do better with immunotherapy. To investigate whether that homogeneity is due to the tumor or to the immune response to the tumor, Spranger is seeking to build a model system. The research involves a lot of costly sequencing—up to $3,000 per attempt, which is fairly expensive for a young lab—and each try has an element of what Spranger half-jokingly describes as “close your eyes and hope it worked.”

“Being able to generate preliminary proof of concept data for high-risk projects is of outstanding importance for any principal investigator,” she says. “However, it is particularly important to have freedom and flexibility early on.”

Boosting potential

Advancing cancer research and supporting the careers of promising faculty were the intentions of Linda Stern and her late husband Howard Stern ’53, SM ’54, whose gift has supported a series of biology professors since 1993. The first appointee to the chair was Tyler Jacks, now director of the Koch Institute.

Linda Stern says her husband, the cofounder and chairman of E-Z-EM, Inc., and a pioneer in the field of medical imaging, gave thoughtfully to many charitable causes. Yet MIT, where he earned undergraduate and graduate degrees in chemical engineering, had a special place in his heart.

“He was very involved and loved MIT,” says Stern, whose own career path included working as a private detective for 28 years. “He made wonderful contacts and got a wonderful education. He was a real heavy hitter when it came to defending the university.”

MIT’s continued excellence in a competitive environment depends on its ability to recognize and retain faculty, nurture careers, support students, and allow for the pursuit of novel ideas. Like the full professorships awarded to tenured faculty members, career development professorships such as the one endowed by the Sterns fund salary, benefits, and a scholarly allowance. These shorter-term (typically three-year) appointments, however, are specifically meant to accelerate the research and career progression of junior professors with exceptional potential.

“The professorship showed me that MIT as a community is invested and interested in fostering my career,” says Spranger. The discretionary funds she receives from the chair can cover, without need for an approval process, expenses that are not paid for by grants or that suddenly arise from a new idea or opportunity. They can keep projects running in tough times, fund travel to conferences, and purchase equipment. “It gives you a little more traction,” Spranger says. “It’s probably the best invested money because you have a lot of ideas you want to test, and at the same time, you are still checking the pulse of where the field might go and where you want to build your niche.”