On a daily basis, multitudes of molecules enter each cell in our body. These can be nutrients or signal molecules or pathogenic microorganisms. An organelle in the cell directs these molecules to other stations for further processing. This organelle is called the endosome.

If the pathways by which this sorting occurs fails at any stage, several diseases such as neurodegenerative diseases and certain cancers can occur. Thus, a better understanding of the steps in these pathways is of utmost importance.

In a recent study published in Communications Biology, a group of scientists from Japan and Austria, led by Prof Jiro Toshima from the Tokyo University of Science, reports a new finding regarding the maintenance and functioning of the endosome.

Conventional knowledge is that two processes are necessary for the upkeep of endosomes: a) sacs of molecules constantly form at the cell membrane, are transported to the endosome, and fuse into it; b) protein-containing vesicles transported from the Golgi (another cell organelle) fuse with the endosome.

The researchers of this study claim that this is not the case.

They introduce genetic mutations and drugs into yeast cells to inhibit each of these transport processes at a time.

When transport from the Golgi does not occur, a protein essential to the upkeep of the endosome, Rab5, is not activated, and endosome formation is affected. When cell transport from the membrane is inhibited, there is no effect on the endosome.

Thus, essentially, transport from the Golgi is necessary and that from the cell membrane is dispensable, or not as crucial. "Our results provide a different view of endosome formation and identify the Golgi as critical for the optimal maintenance and functioning of endosomes," Prof Toshima says.

This study clarifies only a fraction of the molecule-sorting pathway in cells. But, this is certainly one giant step in the research in this field. Perhaps, the insights from this study will soon appear on the pages of cell biology textbooks.

Source:

Journal reference:

Nagano, M. et al. (2019) Rab5-mediated endosome formation is regulated at the trans-Golgi network. Communications Biology. doi.org/10.1038/s42003-019-0670-5.

Link:
New findings regarding maintenance and functioning of the endosome - News-Medical.net

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The Benefits of Molecular Cell Biology - Books LIVE

Inside our cells, natural housekeeping processes are going on every day.

Proteins required for basic life processes carry out this work across all cell types in the body.

But they require regulation. Like a parent endlessly clearing up after teenagers to prevent too much mess accumulating, our cells tightly control levels of this activity to maintain smooth operation.

The most common way of achieving this is by turning on or off genes in response to the need for the housekeeping protein products they create.

This is accomplished via feedback control of transcription the first step in the process of gene expression, by which information from a gene is used to create a functional product like a protein.

A second method is to degrade messenger RNA (mRNA), which acts as an intermediate carrying instructions in the process of turning a gene into a protein. By stopping these messages, less protein is made.

It was almost 40 years ago that researchers noticed that cells monitor the amount of a group of housekeeping proteins called tubulins and adjust levels of tubulin mRNAs accordingly.

This is called autoregulation, but no factors in the feedback process have previously been identified until now.

In the Cell Biology Division of the MRC Laboratory of Molecular Biology, Manu Hegdes lab has discovered a protein used by cells to find unnecessary mRNA and trigger its destruction.

This is significant not just for our understanding of cellular processes, but also in the fight against disease.

Tubulins are key to the structure and function of neurons, and mutations in tubulin genes cause various neurodevelopmental diseases. Drugs used to treat gout and certain cancer types also target tubulin.

This means that the discovery of a factor regulating tubulin could help lead to new therapeutics for such diseases.

Zhewang Lin in Manus lab searched for factors that selectively engage our cells protein-making factories ribosomes when producing tubulin. He discovered a factor called TTC5 that binds only ribosomes actively making tubulin.

Working with Vish Chandrasekaran, in Venki Ramakrishnans group within the LMBs Structural Studies Division, the structure of TTC5 when bound to a tubulin-producing ribosome was then determined.

They found a groove, within which the beginning of tubulin binds as it emerges from the ribosome like an item being captured as it comes off a factory production line.

Zhewang then made mutations in TTC5, which made them unable to regulate tubulin production rates when excess was present. The factory, in other words, was allowed to go into overdrive.

The work indicated how TTC5 uses the emerging protein as a beacon to find tubulin mRNAs for degradation.

Ivana Gasic in Tim Mitchisons lab at Harvard worked with Zhewang to show that if a working TTC5 is not present, meaning a cell cannot fine-tune its tubulin content, then the alignment and segregation of chromosomes is more prone to errors. They believe this is because tubulin plays a critical role in cell division.

It joins together to form microtubules, which control this key cellular event, along with cell movement and cell shape. Precise control of levels of tubulin is therefore vital.

Further experiments by Zhewang showed that TTC5 is not always available. It is normally sequestered hidden by an inhibitor, which has yet to be identified. It releases TTC5 only under conditions when cells detect too much free tubulin.

The researchers now hope to find this inhibitor and understand how it controls this process of sequestering and releasing TTC5.

Manus lab is also working to identify the machinery responsible for degrading mRNA when requested.

But the mechanism of the nascent protein acting like a beacon to find the tubulin mRNA is important.

Manu told the Cambridge Independent: Our discovery of a central component of the thermostat that regulates the production rate of tubulins allows us to begin understanding how such control systems operate inside the cell. Similar mechanisms are probably used to maintain other important proteins at optimal levels to keep cells healthy.

This work was funded by the MRC, the US National Institutes of Health, the Human Frontier Science Program, the Damon Runyon Cancer Research Foundation, Harvard Medical School, the Vallee Scholars Program, the Wellcome Trust, the Agouron Institute, and the Louis-Jeantet Foundation.

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Dr Jan Lwe on the next frontier for MRC Laboratory of Molecular Biology in Cambridge

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Housekeeping secrets of our cells are uncovered by the MRC LMB - Cambridge Independent

In an effort to address the critical public health need for new, safer and more effective medicines to treat pain, a consortium based at the Laboratory of Systems Pharmacology (LSP) at Harvard Medical School has launched an ambitious project titled STOP PAIN (Safe Therapeutic Options for Pain and Inflammation).

By combining a wide range of experimental and artificial intelligence-driven approaches, the consortium aims to identify compounds that selectively block the activity of nociceptors--the sensory neurons that sense and initiate pain--with the goal of developing new, preclinical drug candidates that offer an alternative to the opioid-based medications at the heart of the U.S. opioid epidemic.

The project is led by researchers from HMS and Boston Children's Hospital, with collaborators from Massachusetts Institute of Technology (MIT) and the Max Planck Institute for Medical Research in Germany.

It is supported by the U.S. Defense Advanced Research Projects Agency (DARPA) through the Panacea program, which aims to engender new therapies that address under-met medical needs of active duty soldiers and veterans. The DARPA cooperative agreement includes funding of up to $23,378,281.

The STOP PAIN consortium encompasses expertise across research disciplines, including neurobiology, systems pharmacology, stem cell biology, and computational and medicinal chemistry, and is led by:

We have substantial opportunities today to combine new laboratory methods, advanced chemistry and artificial intelligence and bring those tools to bear on the enormous societal, scientific and medical challenges of pain management.

Modern cancer care, for example, is now full of promising new medicines based on transformative science, yet if we look back two decades the field appeared to be stuck. We hope that advances in the science of sensation and computing will similarly shift the trajectory of drug development for pain."

Peter Sorger

According to the National Institute on Drug Abuse, an estimated 1.7 million Americans suffered from substance use disorders related to prescription opioid pain relievers in 2017 alone, and more than 47,000 died as a result of opioid overdose, leading government agencies to declare a nationwide public health emergency that year.

Prescription opioids are generally effective for the immediate and temporary treatment of severe pain, such as after trauma or surgery. However, they are only partially or not at all effective for chronic pain, and their prolonged use carries serious risks for developing tolerance, addiction and misuse.

Efforts to develop nonopioid pain therapies have been largely unsuccessful, highlighted, for example, by the high-profile recall of the prescription pain and inflammation drug Vioxx in 2014. Currently available medications such as acetaminophen and ibuprofen are not as effective as opioids and, when used long-term, can have adverse side effects that include gastrointestinal bleeding and liver damage.

Due to the lack of viable alternatives, prescription opioids remain a primary therapeutic option for the management of both acute and chronic pain.

"If we can successfully build better drugs to control pain, such that no physician would ever need to prescribe opioids because there would be safer and more effective options available, there would be an enormous impact on both the practice of medicine and on the societal catastrophe that the opioid epidemic has created," Woolf said. "As a consortium, we are keen to accept this challenge and to do everything possible to achieve this goal."

To identify new, nonopioid drug candidates, the STOP PAIN consortium is taking a unique approach that embraces the complexity of the biology of pain.

Current drug development processes in industry typically focus on screening for compounds that affect a single biological target--such as recent failed efforts to develop drugs targeting the protein Nav1.7, identified as defective in people with a congenital disorder that renders them insensitive to pain.

In contrast, the consortium will not begin with predetermined targets but instead focus on the activity of cells, specifically the nociceptor neurons responsible for initiating the sensation of pain.

"This project is based on the recognition that many of the most effective drugs for other neurological diseases have many molecular targets, not just one," Bean said. "Our goal is to systematically understand the complex network of molecules controlling the function of pain-sensing neurons and use that knowledge to design drug molecules that hit many targets, with the aim of safely and selectively inhibiting nociceptor function."

The team will screen for small molecule, nonopioid-based compounds that silence the activity of stem-cell derived human nociceptors under laboratory conditions.

The team will focus on compounds that exclusively block nociceptor function, while leaving the activity of other cell types, such as motor neurons or heart cells, unaffected. This selective targeting is a key preclinical marker of safety and specificity. These compounds then will be comprehensively analyzed for their molecular and biological characteristics, including effects on gene expression, protein production and cell physiology.

These data will be combined with insights drawn from INDRA (Integrated Network and Dynamical Reasoning Assembler), a powerful artificial intelligence system developed at the LSP, which automatically parses the scientific literature and public databases to construct models of gene and protein networks that can then be tested in the lab.

Together, these analyses aim to articulate the precise molecular mechanisms by which compounds inhibit nociceptor function and reveal the specific molecular targets involved in order to inform further drug development.

Once fully characterized, promising compounds will be refined or redesigned through computational and experimental chemistry techniques to maximize their potential efficacy.

The compounds will then be tested for safety and efficacy for pain management in preclinical models and through new machine vision and learning tools developed by the consortium.

By integrating these complementary approaches, the STOP PAIN consortium intends to generate thoroughly evaluated drug candidates for submission to the U.S. Food and Drug Administration for Investigational New Drug designation.

In addition, the team believes that the shift from a target-based approach to a cell-based screening approach backed up by sophisticated computational modeling could help transform the process of drug discovery and validation by offering an alternative model to address other critical unmet therapeutic needs.

Drug development is notoriously slow and arduous, but the researchers say they are optimistic that the depth and breadth of their collective expertise--drawn from multiple disciplines and institutions--makes it possible to develop drug candidates suitable for human clinical trials within the five-year time frame of the project. As one measure of progress, new compounds are already being synthesized and tested by the team.

This project is closely aligned with the recently launched Therapeutics Initiative at HMS, which aims to expedite the translation of basic science discoveries into new treatments for patients.

To this end, the consortium will pursue development of the most promising drug candidates through new ventures or collaborations with existing pharmaceutical or biotech companies. This includes working with life sciences incubators such as the Pagliuca Harvard Life Lab or the recently announced Blavatnik Harvard Life Lab Longwood, which both support early-stage, high-potential biotech and life sciences projects from the Harvard community.

"The development of safer medications to replace prescription opioids for pain management remains one of the most pressing unmet needs in medicine," said George Q. Daley, Dean of HMS. "This ambitious multi-institutional consortium offers promise for improving the health and well-being of countless patients and families."

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Consortium launches ambitious project to transform the treatment of pain - News-Medical.net

LOUISVILLE, Ky.--(BUSINESS WIRE)-- The National Stem Cell Foundation (NSCF) announced today that research teams from Aspen Neuroscience and the New York Stem Cell Foundation (NYSCF) Research Institute will send a first-in-kind study of neurodegenerative disease to the International Space Station (ISS) on the nineteenth SpaceX Commercial Resupply Services (CRS-19) mission, scheduled to launch December 4th from the Kennedy Space Center in Cape Canaveral, Florida. This is the second space flight for the research teams. A preliminary experiment was launched to the ISS in July 2019 onboard SpaceX CRS-18 to test custom flight hardware systems and refine post-flight analytical methods in preparation for the SpaceX CRS-19 launch.

The NSCF-funded collaboration between researchers at the NYSCF Research Institute and Aspen Neuroscience will perform the first study of long-term cell cultures of patient-derived induced pluripotent stem cell (iPSC) neural organoids with microglia on the ISS to study Parkinsons disease and primary progressive multiple sclerosis in microgravity. The ability to observe cell interaction, cell signaling, migration, changes in gene expression and the common pathways of neuroinflammation for both diseases in microgravity provides an opportunity to view the biological processes in a way that is not possible on Earth. This innovative approach to modelling disease has the potential to provide valuable new insight into the fundamental mechanisms underlying neurodegenerative disorders that may accelerate biomarker discovery and potential new drug and cell therapy options for patients. These models also offer potential for better translational study and future personalized medicine applications.

The development of patient-specific, 3-dimensional human organoids that incorporate microglia (the inflammatory cells of the immune system implicated in the development of Parkinsons, MS and other neurodegenerative diseases) for observation and study in the unique research environment of microgravity has the potential to enable progress across the field for a wide variety of conditions that affect a significant portion of the global population. The engineering required to facilitate the transport of cells and culture on orbit is being led by space flight engineering partner Space Tango.

Dr. Paula Grisanti, CEO of NSCF said, Supporting this collaboration between world-class research teams during a time of explosive growth in our understanding of the research advances possible in space is a great privilege. We are delighted to be funding such innovative science at the frontier of new drug and cell therapy discovery.

We are thrilled to be working with such a comprehensive team of scientists and fantastic organizations and feel honored to use our technology to better understand neurodegenerative disorders affecting so many persons globally, said Dr. Andres Bratt-Leal, Vice President of Research and Development, Aspen Neuroscience.

We feel privileged to have the opportunity to help understand the behavior of neural cells in microgravity and to help model neurodegenerative disease in such a novel way. We are excited about this fantastic project and look forward to learning the results, said Dr. Jeanne Loring, Chief Scientific Officer, Aspen Neuroscience.

We are excited to collaborate on the first study of progressive multiple sclerosis and Parkinsons patient brain cells in space. This work will provide important insights into the mechanisms behind these diseases and advance targets for future treatments," noted Susan L. Solomon, NYSCF Chief Executive Officer.

There is significant potential to advance our understanding of MS and PD as we initiate these long-term studies of patient cells in microgravity now that we have completed our preliminary tests, said Dr. Valentina Fossati, NYSCF Senior Research Investigator. We look forward to leveraging the unique capabilities of spaceflight research to better understand the role of microglia in multiple sclerosis and Parkinsons disease, as well as how dysfunction in these cells can be targeted therapeutically.

It takes vision, passion, and courage to change the paradigms of current understanding, said Jana Stoudemire, Commercial Innovation Officer at Space Tango. We are honored to support the groundbreaking work of the National Stem Cell Foundation and these recognized leaders in stem cell biology. Their commitment and dedication to advancing the frontiers of science using new tools and new approaches has been inspiring to witness, and has the potential to provide an entirely new perspective on Parkinsons and progressive MS.

To learn more about this unique collaboration, visit https://www.stemcellsinspace.org/.

About The National Stem Cell Foundation (NSCF)

The National Stem Cell Foundation is a 501(c)3 non-profit organization that funds adult stem cell and regenerative medicine research, connects children with limited resources to clinical trials for rare diseases and underwrites the National STEM Scholar Program for middle school science teachers inspiring the next generation of STEM (science, technology, engineering and math) pioneers nationwide. For more information, visit https://nationalstemcellfoundation.org/.

About The New York Stem Cell Foundation (NYSCF) Research Institute

The New York Stem Cell Foundation Research Institute is an independent organization accelerating cures and better treatments for patients through stem cell research. The NYSCF global community includes over 180 researchers at leading institutions worldwide, including NYSCF Druckenmiller Fellows, NYSCF Robertson Investigators, NYSCF Robertson Stem Cell Prize Recipients, and NYSCF Research Institute scientists and engineers. The NYSCF Research Institute is an acknowledged world leader in stem cell research and in developing pioneering stem cell technologies, including the NYSCF Global Stem Cell Array and in enabling large-scale stem cell research for scientists around the globe. NYSCF focuses on translational research in a model designed to overcome the barriers that slow discovery and replace silos with collaboration. For more information, visit http://www.nyscf.org.

About Aspen Neuroscience, Inc.

Aspen Neuroscience is a development stage, private biotechnology company that uses innovative genomic approaches combined with stem cell biology to deliver patient-specific, restorative cell therapies that modify the course of Parkinsons disease. The pipeline technology of Aspen is based upon the scientific work of world-renowned stem cell scientist, Dr. Jeanne Loring, who has developed a novel method for autologous neuron replacement. For more information and important updates, please visit http://www.aspenneuroscience.com.

About Space Tango, Inc.

Space Tango provides improved access to microgravity through their Open Orbit platform for bioengineering and manufacturing applications that benefit life on Earth. With their first operational TangoLab facility installed on the International Space Station in 2016, and a second facility installed in 2017, Space Tango has designed and flown nearly 80 diverse payloads. As a recognized leader in the development of fully automated, remote-controlled systems for research and manufacturing in orbit, Space Tango continues to provide expertise in technology and scientific consulting for industry and academic partners. Leveraging this current work, Space Tango is developing new commercial market segments in space with the announcement of ST-42 a fully autonomous orbital platform designed specifically for scalable manufacturing in space. Space Tango envisions a future where the next important breakthroughs in both technology and healthcare will occur off the planet, creating a new global market 250 miles up in low Earth orbit. For more information, visit http://www.spacetango.com.

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First-in-kind Human 3-dimensional Models of Parkinson's Disease and Progressive Multiple Sclerosis Launching to the International Space Station -...

A study has demonstrated how mutations in early colon cancer prevail and grow into malignancies, using fluorescent imaging.

Researchers have revealed how stem cell mutations arise and spread throughout a widening field of the colon until they eventually become a malignancy. According to the team, their technique could lead to therapeutic developments and earlier treatment of the disease.

High magnification image of fluorescent intestinal stem cells. Each fluorescent colour is used as a barcode to visualise human colon cancer-causing mutations in mice (credit: Duke Health).

The study was conducted at the Duke Cancer Institute at Duke University, US.

Using an innovative modelling system in mice, the researchers visually tagged colon cancer mutations by causing stem cells to grow. This allowed them to identify the prevailing mutations, which could be visualised in the animals.

The team tagged several common colon cancer mutations in the stem cells of a single tumour to create a fluorescent barcode. When transferred to a mouse, the colours of the stem cells could be tracked, revealing the cellular and molecular dynamics of the pre-cancerous events.

The researchers suggest that their technique can be used to discover field cancerisation, which is suggested to be the defining event that initiates the process of cancer growth.

This study provides new insight into the previously invisible process in which mutant pre-cancerous stem cells spread throughout the colon and seed cancer, said Dr Joshua Snyder, Assistant Professor in the Departments of Surgery and Cell Biology at Duke and corresponding and co-senior author.

Our technique sets a firm foundation for testing new therapies that interrupt this early, pre-malignant process. We hope to one day target and eliminate these stealth precancerous cells to prevent cancer, Snyder continued.

The findings were published in Nature Communications.

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Researchers use imaging to reveal early stages of colon cancer - Drug Target Review

Researchers: Derrick C. Wan, MD, FACS and Arash Momeni, MD, FACS

DURHAM, N.C. (PRWEB) December 03, 2019

A new study released today in STEM CELLS outlines how fat grafting which previous studies have shown can reduce and even reverse fibrosis (scar tissue) buildup also improves the range of motion of the affected limb. The study, conducted by researchers at Stanford University School of Medicine, was conducted on mice.

The tumor-destroying capabilities of radiation therapy can be a life saver for a person suffering from cancer. But its a therapy that has several unwanted side effects, too, including causing substantial damage not just to cancerous cells, but any healthy tissue in its path. Over time, fibrosis builds up in the treated area which, in the case of an arm, shoulder, or leg, for example, can lead to painful contractures that significantly limit extensibility and negatively impact the persons quality of life.

The Stanford team irradiated the right hind legs of subject mice, which resulted in chronic fibrosis and limb contracture. Four weeks later, the irradiated limbs of one group of the mice were injected with fat enriched with stromal vascular cells (SVCs). These potent cells already naturally exist in fat, but supplementation of fat with additional SVCs enhances its regenerative capabilities. A second group was injected with fat only, a third group with saline and a fourth group received no injections, for comparison. The animals ability to extend their limb was then measured at baseline and every two weeks for a 12-week period. At the end of the 12 weeks, the hind limb skin underwent histological analysis and biomechanical strength testing.

Each animal showed significant reduction in its limb extension ability due to the radiation, but this was progressively rescued by fat grafting, reported corresponding author Derrick C. Wan, M.D., FACS. Fat grafting also reduced skin stiffness and reversed the radiation-induced histological changes in the skin.

The greatest benefits were found in mice injected with fat enriched with SVCs, Dr. Wan added. SVCs are easily obtained through liposuction and can be coaxed into different tissue types, where they can support neovascularization, replace cells and repair injured issue.

Our study showed the ability of fat to improve mobility as well as vascularity and appearance, he continued. We think this holds enormous clinical potential especially given that adipose tissue is abundant and can be easily collected from the patients themselves and underscores an attractive approach to address challenging soft tissue fibrosis in patients following radiation therapy.

Furthermore, said co-author and world-renowned breast reconstructive expert Arash Momeni, M.D., FACS, Our observations are potentially translatable to a variety of challenging clinical scenarios. Being able to reverse radiation-induced effects holds promise to substantially improve clinical outcomes in implant-based as well as autologous breast reconstruction. The study findings are indeed encouraging as they could offer patients novel treatment modalities for debility clinical conditions.

Excessive scarring is a challenging problem that is associated with a variety of clinical conditions, such as burn injuries, tendon lacerations, etc. The potential to improve outcomes based on treatment modalities derived from our research is indeed exciting, Dr. Momeni added.

"Skin and soft tissue scarring and fibrosis are well-established problems after radiation. The current study, showing that human fat grafting can normalize the collagen networks and improve tissue elasticity in immune deficient mice, provides molecular evidence for how fat grafting functions, said Dr. Jan Nolta, Editor-in-Chief of STEM CELLS. The studies indicate that, with the appropriate regulatory approvals, autologous fat grafting could potentially also help human patients recover from radiation-induced tissue fibrosis.

The full article, Fat grafting rescues radiation-induced joint contracture, can be accessed at https://stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/stem.3115.

About the Journal: STEM CELLS, a peer reviewed journal published monthly, provides a forum for prompt publication of original investigative papers and concise reviews. The journal covers all aspects of stem cells: embryonic stem cells/induced pluripotent stem cells; tissue-specific stem cells; cancer stem cells; the stem cell niche; stem cell epigenetics, genomics and proteomics; and translational and clinical research. STEM CELLS is co-published by AlphaMed Press and Wiley.

About AlphaMed Press: Established in 1983, AlphaMed Press with offices in Durham, NC, San Francisco, CA, and Belfast, Northern Ireland, publishes three internationally renowned peer-reviewed journals with globally recognized editorial boards dedicated to advancing knowledge and education in their focused disciplines. STEM CELLS (http://www.StemCells.com) is the world's first journal devoted to this fast paced field of research. THE ONCOLOGIST (http://www.TheOncologist.com) is devoted to community and hospital-based oncologists and physicians entrusted with cancer patient care. STEM CELLS TRANSLATIONAL MEDICINE (http://www.StemCellsTM.com) is dedicated to significantly advancing the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and clinical trials, SCTM will help move applications of these critical investigations closer to accepted best practices.

About Wiley: Wiley, a global company, helps people and organizations develop the skills and knowledge they need to succeed. Our online scientific, technical, medical and scholarly journals, combined with our digital learning, assessment and certification solutions, help universities, learned societies, businesses, governments and individuals increase the academic and professional impact of their work. For more than 200 years, we have delivered consistent performance to our stakeholders. The company's website can be accessed at http://www.wiley.com.

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Fat grafting improves range of motion in limbs damaged by radiation therapy - PR Web

Innate Pharma SA (Euronext Paris: IPH ISIN: FR0010331421; Nasdaq: IPHA) today announced its certification as a great work place by the independent institute, Great Place to Work, a global authority on workplace culture, employee experience and leadership behaviors. This recognition was based extensively on ratings provided by Innate Pharma's employees in an anonymous survey that assessed perspectives on leadership, organizational culture and trust.

We are very proud to have obtained the Great Place to Work certification, which acknowledges a high-performing and collaborative culture that attracts, engages and develops its employees," said Mondher Mahjoubi, Chief Executive Officer of Innate Pharma. In the highly competitive biotech industry, our success depends on our ability to foster a positive company culture. Its rewarding to see the time, resources and energy weve committed around collaborating, listening and communicating to employees, reflected in our high levels of employee engagement and recognized by this external validation.

Eighty-six percent of employees participated in the Great Place to Work survey process. Managerial practices, collaborative spirit, working conditions and commitment to the company were identified as main strengths of the company.

"Congratulations to Innate Pharma for being one of the Great Place to Work 2019 certified companies. This innovative company, with a strong social mission, has succeeded in getting employees to support its corporate culture and mission. As such, 90 percent of employees say they are proud to tell others that they are working for Innate Pharma. Thus, the Great Place to Work project, led by the company's highest level of management, contributes to making it a great place to work, said Patrick Dumoulin, President of Great Place to Work France.

About Great Place to Work

Great Place to Work is the global authority on workplace culture.Since 1992, they have surveyed more than 100 million employees around the world and used those deep insights to define what makes a great workplace: trust. Their unparalleled benchmark data is used to recognize Great Place to Work-Certified companies and the Best Workplaces in the US and more than 60 countries, including the 100 Best Companies to Work For and World's Best list published annually in Fortune. Everything they do is driven by the mission to build a better world by helping every organization become a Great Place to Work For All. To learn more, visit greatplacetowork.com.

About Innate Pharma:

Innate Pharma S.A. is a commercial stage oncology-focused biotech company dedicated to improving treatment and clinical outcomes for patients through therapeutic antibodies that harness the immune system to fight cancer.

Innate Pharmas commercial-stage product, Lumoxiti, in-licensed from AstraZeneca in the US, EU and Switzerland, was approved by the FDA in September 2018. Lumoxiti is a first-in class specialty oncology product for hairy cell leukemia. Innate Pharmas broad pipeline of antibodies includes several potentially first-in-class clinical and preclinical candidates in cancers with high unmet medical need.

Innate has been a pioneer in the understanding of natural killer cell biology and has expanded its expertise in the tumor microenvironment and tumor-antigens, as well as antibody engineering. This innovative approach has resulted in a diversified proprietary portfolio and major alliances with leaders in the biopharmaceutical industry including Bristol-Myers Squibb, Novo Nordisk A/S, Sanofi, and a multi-products collaboration with AstraZeneca.

Based in Marseille, France, Innate Pharma is listed on Euronext Paris and Nasdaq in the US.

Learn more about Innate Pharma at http://www.innate-pharma.com

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This press release contains certain forward-looking statements, including those within the meaning of the Private Securities Litigation Reform Act of 1995.The use of certain words, including believe, potential, expect and will and similar expressions, is intended to identify forward-looking statements.Although the company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. These risks and uncertainties include, among other things, the uncertainties inherent in research and development, including related to safety, progression of and results from its ongoing and planned clinical trials and preclinical studies, review and approvals by regulatory authorities of its product candidates, the Companys commercialization efforts and the Companys continued ability to raise capital to fund its development.For an additional discussion of risks and uncertainties which could cause the company's actual results, financial condition, performance or achievements to differ from those contained in the forward-looking statements, please refer to the Risk Factors (Facteurs de Risque") section of the Universal Registration Document filed with the French Financial Markets Authority (AMF), which is available on the AMF website http://www.amf-france.org or on Innate Pharmas website, and public filings and reports filed with the U.S. Securities and Exchange Commission (SEC), including the Companys final prospectus dated October 16, 2019, and subsequent filings and reports filed with the AMF or SEC, or otherwise made public, by the Company.

This press release and the information contained herein do not constitute an offer to sell or a solicitation of an offer to buy or subscribe to shares in Innate Pharma in any country.

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